A prospective observational study of real-world treatment and outcome in secondary CNS lymphoma.

BACKGROUND: Secondary central nervous system lymphoma (SCNSL) confers a dismal prognosis and treatment advances are constrained by the lack of prospective studies and real-world treatment evidence. METHODS: Patients with SCNSL of all entities were included at first diagnosis and patient characteristics, treatment data, and outcomes were prospectively collected in the Secondary CNS Lymphoma Registry (SCNSL-R) (NCT05114330). FINDINGS: 279 patients from 47 institutions were enrolled from 2011 to 2022 and 243 patients (median age: 66 years; range: 23-86) were available for analysis. Of those, 49 (20 %) patients presented with synchronous (cohort I) and 194 (80 %) with metachronous SCNSL (cohort II). The predominant histology was diffuse large B-cell lymphoma (DLBCL, 68 %). Median overall survival (OS) from diagnosis of CNS involvement was 17·2 months (95 % CI 12-27·5), with longer OS in cohort I (60·6 months, 95 % CI 45·5-not estimable (NE)) than cohort II (11·4 months, 95 % CI 7·8-17·7, log-rank test p < 0.0001). Predominant induction regimens included R-CHOP/high-dose MTX (cohort I) and high-dose MTX/cytarabine (cohort II). Rituximab was used in 166 (68 %) of B-cell lymphoma. Undergoing consolidating high-dose therapy and autologous hematopoietic stem cell transplantation (HDT-ASCT) in partial response (PR) or better was associated with longer OS (HR adjusted 0·47 (95 % CI 0·25-0·89), p = 0·0197). INTERPRETATION: This study is the largest prospective cohort of SCNSL patients providing a comprehensive overview of an international real-world treatment landscape and outcomes. Prognosis was better in patients with SCNSL involvement at initial diagnosis (cohort I) and consolidating HDT-ASCT was associated with favorable outcome in patients with PR or better.

2023 updated MASCC/ESMO Consensus recommendations: Prevention of nausea and vomiting following moderately emetic risk antineoplastic agents.

PURPOSE: Review the literature to update the MASCC guidelines from 2015 for controlling nausea and vomiting with systemic cancer treatment of moderate emetic potential. METHODS: A systematic literature review was completed using Medline, Embase, and Scopus databases. The literature search was done from June 2015 to January 2023 of the management of antiemetic prophylaxis for anticancer therapy of moderate emetic potential. RESULTS: Of 342 papers identified, 19 were relevant to update recommendations about managing antiemetic prophylaxis for systemic cancer treatment regimens of moderate emetic potential. Important practice changing updates include the use of emetic prophylaxis based on a triple combination of neurokinin (NK)1 receptor antagonist, 5-HT3 receptor antagonist, and steroids for patients undergoing carboplatin (AUC ≥ 5) and women < 50 years of age receiving oxaliplatin-based treatment. A double combination of 5-HT3 receptor antagonist and steroids remains the recommended prophylaxis for other MEC. Based on the data in the literature, it is recommended that the administration of steroids should be limited to day 1 in moderately emetogenic chemotherapy regimens, due to the demonstration of non-inferiority between the different regimens. More data is needed on the emetogenicity of new agents at moderate emetogenic risk. Of particular interest would be antiemetic studies with the agents sacituzumab-govitecan and trastuzumab-deruxtecan. Experience to date with these agents indicate an emetogenic potential comparable to carboplatin > AUC 5. Future studies should systematically include patient-related risk assessment in order to define the risk of emesis with MEC beyond the emetogenicity of the chemotherapy and improve the guidelines for new drugs. CONCLUSION: This antiemetic MASCC-ESMO guideline update includes new recommendations considering individual risk factors and the optimization of supportive anti-emetic treatments.

Emetic risk classification and evaluation of the emetogenicity of antineoplastic agents-updated MASCC/ESMO consensus recommendation.

PURPOSE: Our goal was to identify new anticancer agents approved by the US Food and Drug Administration (FDA) and the European Medical Agency (EMA) since the 2016 MASCC/ESMO antiemetic update and classify their emetic potential. METHODS: The MASCC/ESMO Expert Panel classified the emetogenicity of the identified new antineoplastic agents based on nonsystematic reviews of randomized controlled trials, analysis of product labeling, and evaluation of emetic classification in other international guidelines and informal consensus. The emetogenic classification system for oral anticancer agents was revised into two emetic risk categories (minimal-low; moderate-high) to be consistent with the system reported by ASCO (American Society of Clinical Oncology) in their 2017 guideline update. The previously employed four emetic risk classification categories for intravenously administered antineoplastic agents were retained for this update. RESULTS: From June 2015 to January 2023, 107 new antineoplastic agents (44 intravenously administered and 63 orally administered agents) were identified. The reported incidence of vomiting varied significantly across studies for many agents, especially for oral anticancer agents. CONCLUSION: The MASCC/ESMO Expert Panel acknowledges the limitations of our efforts to classify the emetic potential of anticancer agents, especially the imprecision associated with oral agents. However, we have attempted to provide a reasonable approximation of the emetic risk associated with new antineoplastic agents by searching the available literature and reviewing other available international antiemetic guidelines.

2023 Updated MASCC/ESMO Consensus Recommendations: prevention of radiotherapy- and chemoradiotherapy-induced nausea and vomiting.

PURPOSE: Radiotherapy and chemoradiotherapy-induced nausea and vomiting (RINV and C-RINV) are common and distressing, and there is a need for guidance for clinicians to provide up to date optimal antiemetic prophylaxis and treatment. Through a comprehensive review of the literature concerning RINV and C-RINV, this manuscript aims to update the evidence for antiemetic prophylaxis and rescue therapy and provide a new edition of recommendations for the MASCC/ESMO antiemetic guidelines for RINV and C-RINV. METHODS: A systematic review of the literature including data published from May 1, 2015, to January 31, 2023, was performed. All authors assessed the literature. RESULTS: The searches yielded 343 references; 37 met criteria for full article review, and 20 were ultimately retained. Only one randomized study in chemoradiation had the impact to provide new recommendations for the antiemetic guideline. Based on expert consensus, it was decided to change the recommendation for the "low emetic risk" category from "prophylaxis or rescue" to "rescue" only, while the drugs of choice remain unchanged. CONCLUSION: As for the previous guideline, the serotonin receptor antagonists are still the cornerstone in antiemetic prophylaxis of nausea and vomiting induced by high and moderate emetic risk radiotherapy. The guideline update provides new recommendation for the management of C-RINV for radiotherapy and concomitant weekly cisplatin. To avoid overtreatment, antiemetic prophylaxis is no longer recommended for the "low emetic risk" category.

Impact of novel agent therapies on immune cell subsets and infectious complications in patients with relapsed/refractory multiple myeloma.

Introduction: Infections are a leading cause of morbidity and mortality in patients with multiple myeloma (MM). Methods: To examine the effects of modern second-generation novel agent therapy on immune cell subsets, in particular CD4+-T-cells, and infectious complications in patients with relapsed/refractory MM (RRMM), we conducted a prospective cohort study in 112 RRMM patients. Results: Substantially decreased CD4+-T-cells <200/µl before initiation of relapse therapy were detected in 27.7% of patients and were associated with a higher number of previous lines of therapy. Relapse therapy with carfilzomib or pomalidomide showed a significant further decrease of CD4+-T-cells. All novel agents led to a significant decrease of B-cell counts. Overall, infections were frequent with 21.3% of patients requiring antibacterial therapy within the first 3 months of relapse therapy, 5.6% requiring hospitalization. However, in the setting of standard antimicrobial prophylaxis in RRMM patients with very low CD4+-T-cells, no significant association of CD4+T-cell count and an increased risk of infection could be detected. Discussion: Our findings imply that reduced CD4+-T-cell numbers and infections are common in patients with RRMM. We also demonstrate an association with the number of previous therapies and certain substances suggesting an increased need for personalized prophylaxis strategies for opportunistic infections in this patient cohort.

Aspirin use and bleeding events during thrombocytopenia after autologous stem-cell transplantation for multiple myeloma.

Background: In patients with cardiovascular (CV) comorbidities that necessitate antiplatelet therapy (APT), its optimal management during chemotherapy-induced thrombocytopenia remains elusive, as the risk of bleeding has to be balanced against the risk of CV events. The purpose of this study was to assess the risk for bleeding with APT during thrombocytopenia in patients with multiple myeloma undergoing high-dose chemotherapy and subsequent autologous stem-cell transplantation (ASCT) with and without acetylsalicylic acid (ASA) as comedication. Methods: We assessed patients who underwent ASCT at the Heidelberg University Hospital between 2011 and 2020 for bleeding events, management strategies for ASA intake during thrombocytopenia, transfusion requirements, and the occurrence of CV events. Results: There were 57/1,113 patients who continued ASA until at least 1 day after ASCT; thus, a continuous platelet inhibition during thrombocytopenia was assumed. Most of the patients (41/57) continued ASA until they had a platelet count of 20-50/nl. This range reflects the kinetics of thrombocytopenia and nondaily measurements of platelets during ASCT. A tendency toward a higher risk for bleeding events in the ASA group was demonstrated (1.9% (control group) vs. 5.3% (ASA), p = 0.082). The risk factors for bleeding in multivariate analysis were the duration of thrombocytopenia < 50/nl, a history of gastrointestinal bleeding, and diarrhea. The factors predicting the duration of thrombocytopenia were age >60 years, a hematopoietic stem-cell transplantation comorbidity index ≥3, and an impaired bone marrow reserve at admission. CV events occurred in three patients; none of them took ASA or had an indication for APT. Conclusions: The intake of ASA until thrombocytopenia with a platelet count of 20-50/nl appears safe, although an elevated risk cannot be excluded. If ASA is indicated for the secondary prevention of CV events, the evaluation of risk factors for bleeding and a prolonged time of thrombocytopenia before conditioning is crucial to adapt the strategy for ASA intake during thrombocytopenia.

Medical Oncology Education in Europe: Equipping Medical Oncologists to Provide the Best Care for Patients with Cancer.

BACKGROUND: High-quality, evidence-based, and practice-relevant education is essential to equip medical oncologists to provide high-quality care for patients with cancer. The need for medical oncology education is growing due to a rapid development of new therapies with novel mechanisms of action. Moreover, the number of patients with cancer is increasing with the rising in incidence and improved survival for some cancers. Access to medical oncology education and training opportunities, particularly in research, varies considerably in different countries and regions. SUMMARY: The European Society for Medical Oncology (ESMO), the European School of Oncology (ESO), and other relevant associations have developed a wide range of opportunities, resources, and measures to increase access to high-quality medical oncology education. Initiatives that are helping to achieve effective and consistent medical oncology education include the ESMO/ASCO (American Society of Medical Oncology) global curriculum in medical oncology. KEY MESSAGES: There is great value in providing wider educational opportunities than local and national training to increase access and, potentially, quality and scope and reduce variations in medical oncology education. Pan-European and global educational initiatives open up the expertise, knowledge, and best practice on different tumour types and cross-sectional topics, such as supportive and palliative care that can be shared between medical oncologists from other countries.

Parainfluenza virus infections in patients with hematological malignancies or stem cell transplantation: Analysis of clinical characteristics, nosocomial transmission and viral shedding.

To assess morbidity and mortality of parainfluenza virus (PIV) infections in immunocompromised patients, we analysed PIV infections in a hematology and stem cell transplantation (SCT) unit over the course of three years. Isolated PIV strains were characterized by sequence analysis and nosocomial transmission was assessed including phylogenetic analysis of viral strains. 109 cases of PIV infection were identified, 75 in the setting of SCT. PIV type 3 (n = 68) was the most frequent subtype. PIV lower respiratory tract infection (LRTI) was observed in 47 patients (43%) with a mortality of 19%. Severe leukopenia, prior steroid therapy and presence of co-infections were significant risk factors for development of PIV-LRTI in multivariate analysis. Prolonged viral shedding was frequently observed with a median duration of 14 days and up to 79 days, especially in patients after allogeneic SCT and with LRTI. Nosocomial transmission occurred in 47 patients. Phylogenetic analysis of isolated PIV strains and combination with clinical data enabled the identification of seven separate clusters of nosocomial transmission. In conclusion, we observed significant morbidity and mortality of PIV infection in hematology and transplant patients. The clinical impact of co-infections, the possibility of long-term viral shedding and frequent nosocomial transmission should be taken into account when designing infection control strategies.

Quality of Online Information on Multiple Myeloma Available for Laypersons.

Online information can increase patients' competence and engagement. However, there are concerns regarding invalid information. Overall, 300 websites and 50 YouTube videos on multiple myeloma (MM) were evaluated. The websites did not differ between the search engines or search ranks. The median time since the last update was 9 months. The 63 unique websites showed a poor general quality (median JAMA score 2 of 4, only 18% with a valid HON certificate). The patient- (user-) focused quality was medium to poor (median sum DISCERN score 41 out of 80 points). The overall reading level was difficult requiring at least a 12th US school grade. The content level was low (median 24 out of 73 points). Sixteen percent contained misleading/wrong facts. Websites provided by foundation/advocacies showed a significantly higher general and patient- (user-) focused quality. For videos, the median time since upload was 18 months. Judged by the HON foundation score ~80% of videos showed a medium general quality. The patient- (user-) focused quality was medium to poor (median sum DISCERN score 43 points). The content level was very low (median 8 points). MM relevant websites and videos showed a medium to low general, patient- (user-) focused and content quality. Therefore, incorporation of quality indices and regular review is warranted.

Netupitant-palonosetron (NEPA) for Preventing Chemotherapy-induced Nausea and Vomiting: From Clinical Trials to Daily Practice.

Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with many anticancer therapies and can negatively impact patients' quality of life and potentially limit the effectiveness of chemotherapy. Currently, CINV can be prevented in most patients with guideline-recommended antiemetic regimens. However, clinicians do not always follow guidelines, and patients often face difficulties adhering to their prescribed treatments. Therefore, approaches to increase guideline adherence need to be implemented. NEPA is the first and only fixed combination antiemetic, composed of netupitant (oral)/fosnetupitant (intravenous) and palonosetron, which, together with dexamethasone, constitute a triple antiemetic combination recommended for the prevention of CINV for patients receiving highly emetogenic chemotherapy and for certain patients receiving moderately emetogenic chemotherapy. Thus, NEPA offers a convenient and straightforward antiemetic treatment that could improve adherence to guidelines. This review provides an overview of CINV, evaluates the accumulated evidence of NEPA's antiemetic activity and safety from clinical trials and real-world practice, and examines the preliminary evidence of antiemetic control with NEPA in daily clinical settings beyond those described in pivotal trials. Moreover, we review the utility of NEPA in controlling nausea and preserving patients' quality of life during chemotherapy, two major concerns in managing patients with cancer.

The Emesis Trial: Depressive Glioma Patients Are More Affected by Chemotherapy-Induced Nausea and Vomiting.

PURPOSE: Glioma patients face a limited life expectancy and at the same time, they suffer from afflicting symptoms and undesired effects of tumor treatment. Apart from bone marrow suppression, standard chemotherapy with temozolomide causes nausea, emesis and loss of appetite. In this pilot study, we investigated how chemotherapy-induced nausea and vomiting (CINV) affects the patients' levels of depression and their quality of life. METHODS: In this prospective observational multicentre study (n = 87), nausea, emesis and loss of appetite were evaluated with an expanded MASCC questionnaire, covering 10 days during the first and the second cycle of chemotherapy. Quality of life was assessed with the EORTC QLQ-C30 and BN 20 questionnaire and levels of depression with the PHQ-9 inventory before and after the first and second cycle of chemotherapy. RESULTS: CINV affected a minor part of patients. If present, it reached its maximum at day 3 and decreased to baseline level not before day 8. Levels of depression increased significantly after the first cycle of chemotherapy, but decreased during the further course of treatment. Patients with higher levels of depression were more severely affected by CINV and showed a lower quality of life through all time-points. CONCLUSION: We conclude that symptoms of depression should be perceived in advance and treated in order to avoid more severe side effects of tumor treatment. Additionally, in affected patients, delayed nausea was most prominent, pointing toward an activation of the NK1 receptor. We conclude that long acting antiemetics are necessary totreat temozolomide-induced nausea.

The Prevention and Treatment of Nausea and Vomiting During Tumor Therapy.

BACKGROUND: Nausea and vomiting are common and distressing side effects of tumor therapy. Despite prophylaxis, 40-50% of patients suffer from nausea, and 20-30% from vomiting. Antiemetic prophylaxis and treatment are therefore of great importance for improving patients' quality of life and preventing sequelae such as tumor cachexia. METHODS: The recommendations presented here are based on international and national guidelines, updated with publications retrieved by a selective search in the PubMed and Cochrane Library databases, with special attention to randomized controlled trials and meta-analyses that have appeared in the past 5 years since the German clinical practice guideline on supportive therapy was published. RESULTS: Risk-adjusted prevention and treatment is based on the identification of treatment-related and patient-specific risk factors, including female sex and younger age. Parenteral tumor therapy is divided into four risk classes (minimal, low, moderate, high), and oral tumor therapy into two (minimal/low, moderate/high). In radiotherapy, the radiation field is of decisive importance. The antiemetic drugs most commonly used are 5-HT3-RA, NK1-RA, and dexamethasone; olanzapine has proven beneficial as an add-on or rescue drug. The use of steroids in patients being treated with drug combinations including checkpoint inhibitors is discussed controversially because of the potentially reduced therapeutic response. Benzodiazepines, dimenhydrinate, and cannabinoids can be used as backup antiemetics. Acupuncture/acupressure, ginger, and progressive muscle relaxation are pos - sible alternative methods. CONCLUSION: Detailed, effective, risk profile-adapted algorithms for the prevention and treatment of nausea and vomiting are now available for patients undergoing classic chemotherapy regimens or combined radiotherapy and chemotherapy. Optimal symptom control for patients undergoing oral tumor therapy over multiple days in the outpatient setting remains a challenge.

Validation of a proxy-reported SARC-F questionnaire for current and retrospective screening of sarcopenia-related functional impairments.

BACKGROUND: The strength, assistance walking, rise from a chair, climb stairs, and falls (SARC-F) questionnaire is a well-established instrument for screening of sarcopenia and sarcopenia-related functional impairments. As it is based on self-reporting, its use precludes patients who are unable to answer the questionnaire as a consequence of severe acute diseases or cognitive impairment. Therefore, we aimed to validate a proxy-reported version of the SARC-F for both ad-hoc as well as retrospective screening for severe sarcopenia-related functional impairments. METHODS: Patients aged ≥60 years completed the SARC-F and performed the short physical performance battery (SPPB) at baseline (T1). Proxies in Cohort A gave a simultaneous assessment of the patients' functional status with the proxy-reported SARC-F at T1 and again, retrospectively, after 3 months (T2). Proxies in Cohort B only completed the SARC-F retrospectively at T2. The questionnaires' performances were assessed through sensitivity/specificity analyses and receiver operating characteristic (ROC) curves. For non-inferiority analyses, results of both the patient-reported and proxy-reported SARC-F were correlated with the SPPB total score as well as the results of the chair-rise test subcategory; the respective correlation coefficients were tested against each other. RESULTS: One hundred and four patients and 135 proxies participated. Using a SPPB score < 9 points as the reference standard, the proxy-reported SARC-F identified patients at high risk for sarcopenia-related functional impairment with a sensitivity of 0.81 (ad-hoc), 0.88 (retrospective Cohort A), and 0.87 (retrospective Cohort B) as well as a specificity of 0.89 (ad-hoc), 0.78 (retrospective Cohort A), and 0.64 (retrospective Cohort B). Areas under the ROC curves were ≥ 0.9 for the ad-hoc proxy-reported SARC-F and the retrospective proxy-reported SARC-F in both cohorts. The proxy-reported SARC-F showed a non-inferior correlation with the SPPB compared with the patient-reported SARC-F for ad-hoc (P = <0.001) as well as retrospective screening for severe sarcopenia-related functional impairment in both Cohorts A (P = 0.007) and B (P = 0.026). CONCLUSIONS: Proxy-reported SARC-F is a valid instrument for both ad-hoc as well as retrospective screening for sarcopenia-related functional impairment and could become the standard tool for evaluating this risk in older adults with severe acute disease, for example, in patients with quickly evolving haematological conditions.

Antiemetics for adults for prevention of nausea and vomiting caused by moderately or highly emetogenic chemotherapy: a network meta-analysis.

BACKGROUND: About 70% to 80% of adults with cancer experience chemotherapy-induced nausea and vomiting (CINV). CINV remains one of the most distressing symptoms associated with cancer therapy and is associated with decreased adherence to chemotherapy. Combining 5-hydroxytryptamine-3 (5-HT3) receptor antagonists with corticosteroids or additionally with neurokinin-1 (NK1) receptor antagonists is effective in preventing CINV among adults receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Various treatment options are available, but direct head-to-head comparisons do not allow comparison of all treatments versus another.  OBJECTIVES: • In adults with solid cancer or haematological malignancy receiving HEC - To compare the effects of antiemetic treatment combinations including NK1 receptor antagonists, 5-HT3 receptor antagonists, and corticosteroids on prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting in network meta-analysis (NMA) - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy • In adults with solid cancer or haematological malignancy receiving MEC - To compare whether antiemetic treatment combinations including NK1 receptor antagonists, 5-HT3 receptor antagonists, and corticosteroids are superior for prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting to treatment combinations including 5-HT3 receptor antagonists and corticosteroids solely, in network meta-analysis - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, conference proceedings, and study registries from 1988 to February 2021 for randomised controlled trials (RCTs). SELECTION CRITERIA: We included RCTs including adults with any cancer receiving HEC or MEC (according to the latest definition) and comparing combination therapies of NK1 and 5-HT3 inhibitors and corticosteroids for prevention of CINV. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We expressed treatment effects as risk ratios (RRs). Prioritised outcomes were complete control of vomiting during delayed and overall phases, complete control of nausea during the overall phase, quality of life, serious adverse events (SAEs), and on-study mortality. We assessed GRADE and developed 12 'Summary of findings' tables. We report results of most crucial outcomes in the abstract, that is, complete control of vomiting during the overall phase and SAEs. For a comprehensive illustration of results, we randomly chose aprepitant plus granisetron as exemplary reference treatment for HEC, and granisetron as exemplary reference treatment for MEC. MAIN RESULTS: Highly emetogenic chemotherapy (HEC) We included 73 studies reporting on 25,275 participants and comparing 14 treatment combinations with NK1 and 5-HT3 inhibitors. All treatment combinations included corticosteroids. Complete control of vomiting during the overall phase We estimated that 704 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with aprepitant + granisetron. Evidence from NMA (39 RCTs, 21,642 participants; 12 treatment combinations with NK1 and 5-HT3 inhibitors) suggests that the following drug combinations are more efficacious than aprepitant + granisetron for completely controlling vomiting during the overall treatment phase (one to five days): fosnetupitant + palonosetron (810 of 1000; RR 1.15, 95% confidence interval (CI) 0.97 to 1.37; moderate certainty), aprepitant + palonosetron (753 of 1000; RR 1.07, 95% CI 1.98  to 1.18; low-certainty), aprepitant + ramosetron (753 of 1000; RR 1.07, 95% CI 0.95 to 1.21; low certainty), and fosaprepitant + palonosetron (746 of 1000; RR 1.06, 95% CI 0.96 to 1.19; low certainty).  Netupitant + palonosetron (704 of 1000; RR 1.00, 95% CI 0.93 to 1.08; high-certainty) and fosaprepitant + granisetron (697 of 1000; RR 0.99, 95% CI 0.93 to 1.06; high-certainty) have little to no impact on complete control of vomiting during the overall treatment phase (one to five days) when compared to aprepitant + granisetron, respectively.  Evidence further suggests that the following drug combinations are less efficacious than aprepitant + granisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): aprepitant + ondansetron (676 of 1000; RR 0.96, 95% CI 0.88 to 1.05; low certainty), fosaprepitant + ondansetron (662 of 1000; RR 0.94, 95% CI 0.85 to 1.04; low certainty), casopitant + ondansetron (634 of 1000; RR 0.90, 95% CI 0.79 to 1.03; low certainty), rolapitant + granisetron (627 of 1000; RR 0.89, 95% CI 0.78 to 1.01; moderate certainty), and rolapitant + ondansetron (598 of 1000; RR 0.85, 95% CI 0.65 to 1.12; low certainty). We could not include two treatment combinations (ezlopitant + granisetron, aprepitant + tropisetron) in NMA for this outcome because of missing direct comparisons.  Serious adverse events We estimated that 35 of 1000 participants experience any SAEs when treated with aprepitant + granisetron. Evidence from NMA (23 RCTs, 16,065 participants; 11 treatment combinations) suggests that fewer participants may experience SAEs when treated with the following drug combinations than with aprepitant + granisetron: fosaprepitant + ondansetron (8 of 1000; RR 0.23, 95% CI 0.05 to 1.07; low certainty), casopitant + ondansetron (8 of 1000; RR 0.24, 95% CI 0.04 to 1.39; low certainty), netupitant + palonosetron (9 of 1000; RR 0.27, 95% CI 0.05 to 1.58; low certainty), fosaprepitant + granisetron (13 of 1000; RR 0.37, 95% CI 0.09 to 1.50; low certainty), and rolapitant + granisetron (20 of 1000; RR 0.57, 95% CI 0.19 to 1.70; low certainty). Evidence is very uncertain about the effects of aprepitant + ondansetron (8 of 1000; RR 0.22, 95% CI 0.04 to 1.14; very low certainty), aprepitant + ramosetron (11 of 1000; RR 0.31, 95% CI 0.05 to 1.90; very low certainty), fosaprepitant + palonosetron (12 of 1000; RR 0.35, 95% CI 0.04 to 2.95; very low certainty), fosnetupitant + palonosetron (13 of 1000; RR 0.36, 95% CI 0.06 to 2.16; very low certainty), and aprepitant + palonosetron (17 of 1000; RR 0.48, 95% CI 0.05 to 4.78; very low certainty) on the risk of SAEs when compared to aprepitant + granisetron, respectively.  We could not include three treatment combinations (ezlopitant + granisetron, aprepitant + tropisetron, rolapitant + ondansetron) in NMA for this outcome because of missing direct comparisons.  Moderately emetogenic chemotherapy (MEC) We included 38 studies reporting on 12,038 participants and comparing 15 treatment combinations with NK1 and 5-HT3 inhibitors, or 5-HT3 inhibitors solely. All treatment combinations included corticosteroids. Complete control of vomiting during the overall phase We estimated that 555 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with granisetron. Evidence from NMA (22 RCTs, 7800 participants; 11 treatment combinations) suggests that the following drug combinations are more efficacious than granisetron in completely controlling vomiting during the overall treatment phase (one to five days): aprepitant + palonosetron (716 of 1000; RR 1.29, 95% CI 1.00 to 1.66; low certainty), netupitant + palonosetron (694 of 1000; RR 1.25, 95% CI 0.92 to 1.70; low certainty), and rolapitant + granisetron (660 of 1000; RR 1.19, 95% CI 1.06 to 1.33; high certainty).  Palonosetron (588 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) and aprepitant + granisetron (577 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) may or may not increase complete response in the overall treatment phase (one to five days) when compared to granisetron, respectively. Azasetron (560 of 1000; RR 1.01, 95% CI 0.76 to 1.34; low certainty) may result in little to no difference in complete response in the overall treatment phase (one to five days) when compared to granisetron. Evidence further suggests that the following drug combinations are less efficacious than granisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): fosaprepitant + ondansetron (500 of 100; RR 0.90, 95% CI 0.66 to 1.22; low certainty), aprepitant + ondansetron (477 of 1000; RR 0.86, 95% CI 0.64 to 1.17; low certainty), casopitant + ondansetron (461 of 1000; RR 0.83, 95% CI 0.62 to 1.12; low certainty), and ondansetron (433 of 1000; RR 0.78, 95% CI 0.59 to 1.04; low certainty). We could not include five treatment combinations (fosaprepitant + granisetron, azasetron, dolasetron, ramosetron, tropisetron) in NMA for this outcome because of missing direct comparisons.  Serious adverse events We estimated that 153 of 1000 participants experience any SAEs when treated with granisetron. Evidence from pair-wise comparison (1 RCT, 1344 participants) suggests that more participants may experience SAEs when treated with rolapitant + granisetron (176 of 1000; RR 1.15, 95% CI 0.88 to 1.50; low certainty). NMA was not feasible for this outcome because of missing direct comparisons.  Certainty of evidence Our main reason for downgrading was serious or very serious imprecision (e.g. due to wide 95% CIs crossing or including unity, few events leading to wide 95% CIs, or small information size). Additional reasons for downgrading some comparisons or whole networks were serious study limitations due to high risk of bias or moderate inconsistency within networks. AUTHORS' CONCLUSIONS: This field of supportive cancer care is very well researched. However, new drugs or drug combinations are continuously emerging and need to be systematically researchedand assessed. For people receiving HEC, synthesised evidence does not suggest one superior treatment for prevention and control of chemotherapy-induced nausea and vomiting.  For people receiving MEC, synthesised evidence does not suggest superiority for treatments including both NK1 and 5-HT3 inhibitors when compared to treatments including 5-HT3 inhibitors only. Rather, the results of our NMA suggest that the choice of 5-HT3 inhibitor may have an impact on treatment efficacy in preventing CINV.  When interpreting the results of this systematic review, it is important for the reader to understand that NMAs are no substitute for direct head-to-head comparisons, and that results of our NMA do not necessarily rule out differences that could be clinically relevant for some individuals.

Carfilzomib, Lenalidomide, and Dexamethasone Followed by Salvage Autologous Stem Cell Transplant with or without Maintenance for Relapsed or Refractory Multiple Myeloma.

Salvage high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) is a treatment option for relapsed and/or refractory multiple myeloma (RRMM). No data are available on salvage HDCT/ASCT following re-induction treatment with state-of-the-art triplet regimens. We retrospectively report on 44 patients receiving salvage HDCT/ASCT following re-induction with carfilzomib/lenalidomide/dexamethasone (KRd). All patients received frontline HDCT/ASCT with median time to progression (TTP1) of 2.9 (1.2-13.5) years, enabling paired comparison of frontline and salvage HDCT/ASCT. After re-induction and before salvage transplant, 25/44 patients (57%) attained ≥ very good partial response (VGPR), which increased to 34/44 (77%) at best response after salvage HDCT/ASCT. Median progression-free survival (PFS) was 23.3 months from salvage HDCT/ASCT. Patients with ≥ VGPR at the time of salvage HDCT/ASCT and those receiving maintenance treatment post salvage HDCT/ASCT had significantly superior PFS (hazard ratio (HR) 0.19, p = 0.001 and HR 0.20, p = 0.009). In patients achieving at least an equal depth of response before salvage HDCT/ASCT as before frontline HDCT/ASCT, PFS after salvage HDCT/ASCT was comparable to the frontline situation (p = 0.3). This is the first report of state-of-the-art triplet re-induction and salvage HDCT/ASCT for RRMM after frontline transplantation. Deep remissions achieved with KRd translate into prolonged PFS following salvage HDCT/ASCT and are enhanced by maintenance treatment.

Local Radiation Therapy Before and During Induction Delays Stem Cell Mobilization and Collection in Multiple Myeloma Patients.

In multiple myeloma, local radiation therapy (RT) of osseous lesions before peripheral blood stem cell (PBSC) mobilization is assumed to impair the PBSC mobilization and collection. However, the results of previously published studies are inconsistent and do not evaluate detailed metrics of RT and PBSC outcome parameters. In total, 352 patients undergoing PBSC mobilizations and RT in first-line treatment were evaluated. Patients were grouped into RT (n = 283) and no RT (n = 69) before PBSC mobilization. Except for the International Staging System score, both groups were homogeneous regarding the first diagnosis characteristics, first-line treatments, and response parameters. RT metrics (RT yes versus no, volume of irradiated hematopoietic bone marrow [BM], biologically equivalent doses in 2 Gy fractions [EQD2]) were analyzed for the following PBSC outcome parameters: achievement of the PBSC collection goal, CD34+ cell collection yield, duration of the mobilization phase, and number of leukapheresis (LP) sessions to reach the collection goal. No statistically significant differences in the percentage of collection failures to reach at least 3 sufficient PBSC transplants were identified comparing patients with (n = 32 [11%]) and without RT (n = 4 [6%]) before PBSC mobilization (P = .265). However, patients with RT before PBSC mobilization showed a significant prolongation of the PBSC mobilization (median 1 day, P =.026) and required a higher number of LP sessions to reach the collection goal (median 1 LP, P < .001) compared with patients who received RT after PBSC mobilization. Moreover, patients with RT before PBSC mobilization reached a significantly lower CD34+ cell collection result (mean 8.94 versus 9.81 × 106/kg body weight [bw], P = .002). No correlation was identified between the overall CD34+ cell yield and the volume of irradiated hematopoietic BM or EQD2, respectively. In the RT before PBSC mobilization group, patients who required more than 1 LP session to reach the PBSC collection goal after RT had a significantly higher percentage of radiated hematopoietic BM compared to those who required only 1 LP session (mean 9.7% versus 7.2%, P = .002). Overall, our study indicates a negative impact of RT on PBSC mobilization and collection. Apart from emergency settings, it might be beneficial to postpone RT to a post-PBSC collection time point. © 2021 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Antibiotic Prophylaxis or Granulocyte-Colony Stimulating Factor Support in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

We compare, in this manuscript, antibiotic prophylaxis versus granulocyte-colony stimulating factor (G-CSF) support as anti-infective strategies, in patients with multiple myeloma (MM), undergoing high-dose therapy followed by autologous stem cell transplantation (HDT/ASCT). At our institution, antibiotic prophylaxis after HDT/ASCT in MM was stopped in January 2017 and replaced by G-CSF support in March 2017. Consecutive MM patients who received HDT/ASCT between March 2016 and July 2018 were included in this single-center retrospective analysis. In total, 298 patients and 353 individual cases of HDT/ASCT were evaluated. In multivariate analyses, G-CSF support was associated with a significantly shortened duration of severe leukopenia < 1/nL (p < 0.001, hazard ratio (HR) = 16.22), and hospitalization (estimate = -0.19, p < 0.001) compared to antibiotic prophylaxis. Rates of febrile neutropenia, need of antimicrobial therapy, transfer to intensive care unit, and death, were similar between the two groups. Furthermore, antibiotic prophylaxis was associated with a significantly increased risk for the development of multidrug resistant bacteria especially vancomycin-resistant Enterococcus faecium compared to G-CSF support (odds ratio (OR) = 17.38, p = 0.01). Stop of antibiotic prophylaxis as an anti-infective strategy was associated with a reduction in overall resistance rates of bacterial isolates. These results indicate that G-CSF support should be the preferred option in MM patients undergoing HDT/ASCT.

Practice Patterns for Prevention of Chemotherapy-Induced Nausea and Vomiting and Antiemetic Guideline Adherence Based on Real-World Prescribing Data.

BACKGROUND: Guideline-recommended antiemetic prophylaxis improves nausea and vomiting control in most patients undergoing chemotherapy. Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology (MASCC/ESMO) antiemetic guidelines recommend prophylaxis with a neurokinin-1 receptor antagonist (NK1 RA), a 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), and dexamethasone for patients receiving highly emetogenic chemotherapy (HEC), including anthracycline-cyclophosphamide (AC)- and carboplatin (considered moderately emetogenic chemotherapy)-based chemotherapy. Here, we analyze the use of NK1 RA-5-HT3 RA-dexamethasone for antiemetic prophylaxis associated with HEC and carboplatin. METHODS: The data source was the Global Oncology Monitor (Ipsos Healthcare). Geographically representative physicians from France, Germany, Italy, Spain, and the U.K. were screened for treatment involvement and number of patients treated per month. Patients' data from January to December 2018 were collected from medical charts and extrapolated on the basis of the total number of physicians who prescribe chemotherapy. The emetic risk of chemotherapy was classified per MASCC/ESMO guidelines. RESULTS: Data from 45,324 chemotherapy-treated patients were collected, representing a total extrapolated prevalence of 1,394,848 chemotherapy treatments included in the analysis. NK1 RAs were used in 45%, 42%, and 19% of patients receiving cisplatin-, AC-, and carboplatin-based chemotherapy, respectively; 18%, 24%, and 7% received the guideline-recommended NK1 RA-5-HT3 RA-dexamethasone combination; no antiemetics were prescribed for 12% of the treatments. Often, physicians' perception of the emetic risk of chemotherapy did not follow MASCC/ESMO guideline classification. CONCLUSION: Low adherence to antiemetic guidelines was revealed in clinical practice in five European countries, with 15% of all HEC-/carboplatin-based treatments receiving guideline-recommended NK1 RA-5-HT3 RA-dexamethasone prophylaxis and 12% of them receiving no antiemetics. New strategies for improving guideline adherence are urgently needed. IMPLICATIONS FOR PRACTICE: Despite recent advances in antiemetic therapy, a substantial proportion of patients experience nausea and vomiting associated with chemotherapy in daily clinical practice. Antiemetic guidelines aim at prevention of chemotherapy-induced nausea and vomiting (CINV), and guideline-consistent antiemetic therapy can effectively prevent vomiting and, to a lesser extent, nausea in most patients with cancer. This study reports low adherence to antiemetic guidelines in the highly emetogenic chemotherapy setting in daily clinical practice across five European countries. Opportunity exists to increase adherence to antiemetic guideline recommendations. Implementation of strategies to facilitate guideline adherence can potentially improve CINV control.