Cancer population norms using a new value set for the SF-6Dv2 based on the preferences of patients with breast or colorectal cancer in Quebec.

BACKGROUND: Because health resources are limited, health programs should be compared to allow the most efficient ones to emerge. To that aim, health utility instruments have been developed to allow the calculation of quality-adjusted life-year (QALY). However, generic instruments, which can be used by any individual regardless of their health profile, typically consider the preferences of the general population when developing their value set. Consequently, they are often criticized for lacking sensitivity in certain domains, such as cancer. In response, the latest version of the Short Form 6-Dimension (SF-6Dv2) has been adapted to suit the preferences of patients with breast or colorectal cancer in the Canadian province of Quebec. By extension, our study's aim was to determine cancer population norms of utility among patients with breast or colorectal cancer in Quebec using the SF-6Dv2. METHOD: To determine the cancer population norms, we exploited the data that were used in the development of a new value set for the SF-6Dv2. This value set was developed considering the preferences of patients with breast or colorectal cancer. Stratification by time of data collection (i.e., T1 and T2), sociodemographic variables (i.e., age, sex, body mass index, and self-reported health problems affecting quality of life), and clinical aspects (i.e., cancer site, histopathological classification, cancer stage at diagnosis, modality, and treatment characteristics) was performed. RESULTS: In 353 observations, patients were more likely to have negative utility scores at T1 than at T2. Males had higher mean utility scores than females considering type of cancer and comorbidities. Considering the SF-6Dv2's dimensions, more females than males reported having health issues, most which concerned physical functioning. Significant differences by sex surfaced for all dimensions except "Role Limitation" and "Mental health." Patients with multifocal cancer had the highest mean and median utility values in all cancer sites considered. CONCLUSION: Cancer population norms can serve as a baseline for interpreting the scores obtained by a given population in comparison to the situation of another group. In this way, our results can assist in comparing utility scores among cancer patients with different sociodemographic groups to other patients/populations groups. To our knowledge, our identified utility norms are the first for patients with breast or colorectal cancer from Quebec.

Second Version of the Short Form 6-Dimension Value Set Elicited From Patients With Breast and Colorectal Cancer: A Hybrid Approach.

BACKGROUND: Quality-adjusted life-year instruments help comparison among programs by capturing their effects in terms of utility. Generic instruments are applicable to everyone, and for this reason, they are known to lack sensitivity when measuring gains in some domains. Specific instruments tend to fill this gap but, in domains like cancer, existing instruments are either nonpreferences-based or based on the general population's preferences. PATIENTS AND METHODS: This study describes the development of a new value set for a well-known and highly used generic instrument, the Second Version of the Short Form 6-Dimension, to better consider the preferences of patients with cancer. In this aim, a hybrid approach combining the time trade-off and the discrete choice experiment was used. The population of interest was the Quebec population, Canada, with breast or colorectal cancer. Their preferences were elicited in 2 periods: before (T1) and 8 days after the beginning of a chemotherapy procedure (T2). RESULTS: A total of 2808 observations for the time trade-off and 2520 observations for the discrete choice experiment were used. The parsimonious model encompassing the 2 periods was the preferred model. The new value set allows a greater utility range than the EQ-5D-5L and the Second Version of the Short Form 6-Dimension reference value sets and helps in better considering patients experiencing severe health situations. A good correlation between these 2 instruments and other specific cancer instruments (ie, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, QLU-C10D, and Functional Assessment of Cancer Therapy-General) was observed. Significative differences in utility values were also noted within periods and types of cancer.

Application of the Failure Mode and Effects Analysis (FMEA) to identify vulnerabilities and opportunities for improvement prior to implementing a computerized prescription order entry (CPOE) system in a university hospital oncology clinic.

INTRODUCTION: Prior to implementing a new computerized prescription order entry (CPOE) application, the potential risks associated with this system were assessed and compared to those of paper-based prescriptions. The goal of this study is to identify the vulnerabilities of the CPOE process in order to adapt its design and prevent these potential risks. METHODS AND MATERIALS: Failure mode and effects analysis (FMEA) was used as a prospective risk-management technique to evaluate the chemotherapy medication process in a university hospital oncology clinic. A multidisciplinary team assessed the process and compared the critical steps of a newly developed CPOE application versus paper-based prescriptions. The potential severity, occurrence and detectability were assessed prior to the implementation of the CPOE application in the clinical setting. RESULTS: The FMEA led to the identification of 24 process steps that could theoretically be vulnerable, therefore called failure modes. These failure modes were grouped into four categories of potential risk factors: prescription writing, patient scheduling, treatment dispensing and patient follow-up. Criticality scores were calculated and compared for both strategies. Three failure modes were prioritized and led to modification of the CPOE design. Overall, the CPOE pathway showed a potential risk reduction of 51% compared to paper-based prescriptions. CONCLUSION: FMEA was found to be a useful approach to identify potential risks in the chemotherapy medication process using either CPOE or paper-based prescriptions. The e-prescription mode was estimated to result in less risk than the traditional paper mode.

Pomalidomide, bortezomib, and dexamethasone at first relapse in lenalidomide-pretreated myeloma: A subanalysis of OPTIMISMM by clinical characteristics.

OBJECTIVE: We evaluated the efficacy and safety of pomalidomide, bortezomib, and dexamethasone (PVd) vs bortezomib and dexamethasone (Vd) by age, renal function, and high-risk cytogenetic abnormalities in lenalidomide-pretreated patients with multiple myeloma at first relapse. METHODS: OPTIMISMM was a phase 3, multicenter, open-label, randomized study (NCT01734928; N = 559). The primary endpoint was progression-free survival (PFS). RESULTS: Overall, 226 patients had received one prior line of therapy. PVd significantly prolonged PFS vs Vd in patients aged ≤65 years (median, 22.0 vs 13.1 months; P = .0258) and >65 years (median, 17.6 vs 9.9 months; P = .0369). Median PFS in patients with renal impairment (RI; creatinine clearance <60 mL/min) was 15.1 months with PVd vs 9.5 months with Vd (hazard ratio [HR], 0.67 [95% CI, 0.34-1.34]). In patients without RI, median PFS was 22.0 vs 13.1 months (HR, 0.45 [95% CI, 0.27-0.76]). In patients with high-risk cytogenetics, median PFS was 14.7 vs 9.9 months (HR, 0.39 [95% CI, 0.13-1.17]). PVd significantly improved overall response rate vs Vd in all subgroups. The safety profile of PVd was consistent with previous reports. CONCLUSIONS: These findings confirmed the benefits of PVd at first relapse, including in patients with poor prognostic factors.

Effect of a mixed-exercise program on physical capacity and sedentary behavior in older adults during cancer treatments.

BACKGROUND: Aging, cancer and its treatment all contribute to increase the risk of deconditioning and sedentary behaviors. Mixed exercise is recognized to counteract the effects of aging and deconditioning as well as improving physical capacity during cancer treatment in adults. AIMS: To determine the impact of a mixed exercise program (MXEP) to improve physical capacity and decrease sedentary behavior time (SBT) in older adults during cancer treatment. METHODS: Fourteen participants (68.8 ± 3.4 years) completed 12 weeks of a mixed exercise program (MEXP) (n = 6) or stretching (n = 8) while they were under cancer treatment. Five tests of the Senior Fitness Test (Chair Stand, 8-Foot Up & Go, Arm Curl, Sit & Reach, 6 min Walk Test), two maximal strength tests (leg press and handgrip) and a Global Physical Capacity Score (GPCS) were used to assess physical capacity. For the amount of SBT (min/day), we used question 1 of the Physical Activity Scale for the Elderly. RESULTS: Both groups presented significant pre- vs post-intervention differences for the Chair Stand, Arm Curl, 6 min Walk Tests and also GPCS. Nevertheless, this difference was significantly greater in the MEXP group only for the Chair Stand Test (4.3 ± 2.2 vs 1.0 ± 1.3 reps; p = 0.01) and the GPCS (4.0 ± 0.6 vs 1.5 ± 2.3 points; p = 0.047). A tend to display a greater decrease in SBT (- 295 ± 241 min/week vs - 11 ± 290 min/week; p = 0.079) was observed in favor of MEXP. CONCLUSION: A 12-week mixed exercise program led to significant improvements in physical capacity and may reduce SBT.

Axitinib-induced acute pancreatitis: a case report.

Axitinib is an oral second-generation selective inhibitor of vascular endothelial growth factor receptors recently approved for the treatment of advanced renal cell carcinoma. Numerous cases of acute pancreatitis have been reported after treatment with nonselective tyrosine kinase inhibitors such as sorafenib and sunitinib. We present the first report of a patient under axitinib treatment presenting with acute pancreatitis for which no other etiology has been found. The patient was a 29-year-old woman treated for renal cell carcinoma. The patient had no history of chronic illness, gallstone-related disease, or alcohol consumption. She had been previously treated with sunitinib and everolimus. Four months after the onset of axitinib treatment she was hospitalized for acute pancreatitis. Symptoms and blood lipase levels normalized within a few days after axitinib was withheld. We believe that acute pancreatitis should be recognized as a potential axitinib-related adverse event.

The Mechanisms Underlying the Beneficial Impact of Aerobic Training on Cancer-Related Fatigue: A Conceptual Review.

Cancer-related fatigue (CRF) is a prevalent and persistent issue affecting cancer patients, with a broad impact on their quality of life even years after treatment completion. The precise mechanisms underlying CRF remain elusive, yet its multifaceted nature involves emotional, physical, and cognitive dimensions. The absence of effective medical treatments has prompted researchers to explore integrative models for potential insights. Notably, physical exercise emerges as a promising strategy for managing CRF and related symptoms, as studies showed a reduction in CRF ranging from 19% to 40%. Current recommendations highlight aerobic training at moderate intensity as beneficial, although questions about a dose-response relationship and the importance of exercise intensity persist. Despite the positive impact of exercise on CRF, the underlying mechanisms remain elusive. This review aims to provide a theoretical model explaining how aerobic exercise may alleviate CRF. Focusing on acute exercise effects, this review delves into the potential influence on peripheral and neural inflammation, immune function dysregulation, and neuroendocrine system disruptions. The objective is to enhance our understanding of the intricate relationship between exercise and CRF, ultimately paving the way for tailored interventions and potential pharmacological treatments for individuals unable to engage in physical exercise.

A Real-World Retrospective Analysis of the Management of Advanced Urothelial Carcinoma in Canada.

Locally advanced or metastatic urothelial carcinoma (aUC) presents a significant challenge with high mortality rates. Platinum-based chemotherapy remains the established frontline standard of care, and a switch-maintenance strategy with immunotherapy has now emerged as a new standard for aUC patients without disease progression, following initial platinum therapy. Examining the treatment patterns is imperative, given the evolving therapeutic landscape. In this study, we conducted a retrospective medical chart review of 17 Canadian oncologists treating patients with aUC to assess unmet needs in Canadian aUC patient care. Data from 146 patient charts were analyzed, revealing important clinical insights about the management of aUC. A substantial proportion of patients (53%) presented with de novo metastatic disease, which was possibly influenced by pandemic-related care disruptions. Variability was evident in the cisplatin eligibility criteria, with a majority (70%) of oncologists utilizing a 50 mL/min threshold. Most favored four cycles of platinum-based chemotherapy to spare the bone marrow for future therapies and prevent patient fatigue. Notably, some eligible patients were kept under surveillance rather than receiving maintenance therapy, suggesting a potential gap in awareness regarding evidence-based recommendations. Furthermore, managing treatment-related adverse events was found to be one of the biggest challenges in relation to maintenance immunotherapy. In conclusion, our findings provide the first comprehensive overview of aUC treatment patterns in Canada following the approval of maintenance immunotherapy, offering insights into the decision-making process and underscoring the importance of evidence-based guidelines in aUC patient management.

Acute natural killer cells response to a continuous moderate intensity and a work-matched high intensity interval exercise session in metastatic cancer patients treated with chemotherapy.

Background: It has been suggested that the acute natural killer (NK) cell response to aerobic exercise might contribute to the tumor suppressor effect of regular exercise observed in preclinical studies. Moreover, because this response is modulated by exercise intensity, high-intensity intervals exercise (HIIE) might represent an interesting therapeutic approach in cancer patients. However, this immune response remains unstudied in cancer patients currently undergoing chemotherapy. Objective: To characterize the acute NK cell response following a moderate-intensity continuous aerobic exercise session (MOD), and a HIIE session in metastatic cancer patients treated with chemotherapy. Methods: Twelve cancer patients (45-65 years old) underwent a MOD and a duration and work-matched HIIE trial, in a block-randomized order. Peripheral blood mononuclear cells (PBMC) were isolated before, after and 1h after each trial. NK cell subsets were enumerated using flow cytometry and complete blood counts. The surface expression of the cytotoxic NK cell (cNK; CD56dimCD16+) subset was evaluated for its expression of the differentiation markers CD57 and CD158a, the activating receptor NKG2D, the immune checkpoints TIM-3 and PD-1, and the chemokine receptors CXCR3, CXCR4 and CCR2. Results: cNK cell blood counts increased immediately following MOD (p < 0.001) and decreased back to pre-exercise values 1 h after exercise cessation (p < 0.001). The most responsive cNK cell subsets were expressing CD57, CD158a, NKG2D, TIM-3 and CXCR3. The HIIE trial elicited a similar biphasic response, without any difference between trials (all p ≥ 0.38). However, significant changes in the MFI values of CXCR4 and NKG2D were observed in the cNK cell subset following HIIE (all p ≤ 0.038), but not MOD. Conclusion: In metastatic cancer patients undergoing chemotherapy, both MOD and HIIE can elicit an acute mobilisation and egress of NK cells exhibiting phenotypic characteristics associated with high cytotoxicity and tumor homing. Future longitudinal trials are needed to determine if combining aerobic exercise training and chemotherapy will translate towards favorable immune and clinical outcomes.

Unusual Cases of Monoclonal Gammopathy of Renal Significance.

Introduction: Monoclonal gammopathy of renal significance (MGRS) is a rare entity describing patients with renal impairment related to the secretion of immunoglobulins without hematological criteria for treatment of a specific disease. We present 3 cases of MGRS identified at our center that were either rare or difficult to diagnose. Case Presentations. The first patient presented with monoclonal membranoproliferative glomerulonephritis in the context of known chronic lymphocytic leukemia (CLL), diagnosed about 10 years prior. She presented with nephritic syndrome with serum protein electrophoresis revealing an IgG/lambda peak of less than 1 g/L, stable from the last few years. A renal biopsy confirmed a diagnosis of monoclonal membranoproliferative glomerulonephritis with granular IgG and C3 deposits of various sizes. The second patient presented with renal TMA in the context of IgM MGUS. The patient was admitted for acute nephritic syndrome and thrombotic microangiopathy. Serum protein electrophoresis demonstrated IgM/kappa paraprotein at 1.8 g/L, with a kappa/lambda ratio of 5.48. Renal biopsy demonstrated endocapillary proliferative glomerulonephritis associated with the presence of numerous monotypic IgM/kappa intracapillary pseudothrombi. Characteristic changes of thrombotic microangiopathy were also described. The third patient presented with immunotactoid glomerulonephritis likely from small B-cell lymphoma that later transformed to DLBCL. The patient presented with acute renal failure with IgM/kappa paraprotein of less than 1 g/L on electrophoresis and with a kappa/lambda ratio of 7.09. A diagnosis of immunotactoid glomerulonephritis was made on renal biopsy. Bone marrow with limited specimen revealed a B-cell infiltrate. Biopsy of a breast lesion was compatible with diffuse large B-cell lymphoma (DLBCL). Lymphomatous cells expressed IgM/kappa, thus confirming paraprotein-associated renal lesion. Conclusion: We described 3 different cases of MGRS, highlighting the diversity of renal pathohistological presentations and different associated lymphoproliferative disorders. Biopsy should rapidly be considered, as early diagnosis of MGRS is essential to initiate clone-directed therapy promptly to prevent progression to ESRD or hematologic progression to malignancy.

Poor outcome despite modern treatments: A retrospective study of 99 patients with primary and secondary plasma cell leukemia.

BACKGROUND: Plasma cell leukemia (PCL) is a rare monoclonal gammopathy, associated with short survival. Because of its very low incidence, only a few cohorts have been reported and thus, information on this disease is scarce. The goal of this study was to better understand the clinical features, prognostic factors, and efficacy of modern treatments in both primary PCL (pPCL) and secondary PCL (sPCL). METHODS: We performed a retrospective, multicenter study of patients diagnosed with PCL, defined as circulating plasma cells ≥20% of total leukocytes and/or ≥2 × 109/L. RESULTS: We identified 99 eligible PCL patients, of whom 33 were pPCL and 66 were sPCL. The median progression-free survival (PFS) to frontline treatment and overall survival (OS) were, respectively, 4.8 (95% CI, 0.4-9.2) and 18.3 months (95% CI, 0.0-39.0) for pPCL and 0.8 (95% CI, 0.5-1.1) and 1.2 months (95% CI, 0.9-1.5) for sPCL (both p < 0.001). We observed no improvement in OS over time (2005-2012 vs. 2013-2020, p = 0.629 for pPCL and p = 0.329 for sPCL). Finally, our data suggested that sPCL originates from a high-risk multiple myeloma (MM) population with a short OS (median 30.2 months), early relapse after stem cell transplant (median 11.9 months) and a high proportion of patients with multiple cytogenetic abnormalities (36% with ≥2 abnormalities). CONCLUSIONS: This study is one of the largest PCL cohorts reported. We are also the first to investigate characteristics of MM before its transformation into sPCL and demonstrate that high-risk biologic features already present at the time of MM diagnosis. Moreover, our data highlights the lack of improvement in PCL survival in recent years and the urgent need for better treatment options.

Intrapatient Intermetastatic Heterogeneity Determined by Triple-Tracer PET Imaging in mCRPC Patients and Correlation to Survival: The 3TMPO Cohort Study.

Intrapatient intermetastatic heterogeneity (IIH) has been demonstrated in metastatic castration-resistant prostate cancer (mCRPC) patients and is of the utmost importance for radiopharmaceutical therapy (RPT) eligibility. This study was designed to determine the prevalence of IIH and RPT eligibility in mCRPC patients through a triple-tracer PET imaging strategy. Methods: This was a multisite prospective observational study in which mCRPC patients underwent both 18F-FDG and 68Ga-prostate-specific membrane antigen (PSMA)-617 PET/CT scans. A third scan with 68Ga-DOTATATE, a potential biomarker of neuroendocrine differentiation, was performed if an 18F-FDG-positive/68Ga-PSMA-negative lesion was found. Per-tracer lesion positivity was defined as having an uptake at least 50% above that of the liver. IIH prevalence was defined as the percentage of participants having at least 2 lesions with discordant features on multitracer PET. Results: IIH was observed in 81 patients (82.7%), and at least 1 18F-FDG-positive/68Ga-PSMA-negative lesion was found in 45 patients (45.9%). Of the 37 participants who also underwent 68Ga-DOTATATE PET/CT, 6 (16.2%) had at least 1 68Ga-DOTATATE-positive lesion. In total, 12 different combinations of lesion imaging phenotypes were observed. On the basis of our prespecified criteria, 52 (53.1%) participants were determined to be eligible for PSMA RPT, but none for DOTATATE RPT. Patients with IIH had a significantly shorter median overall survival than patients without IIH (9.5 mo vs. not reached; log-rank P = 0.03; hazard ratio, 2.7; 95% CI, 1.1-6.8). Conclusion: Most mCRPC patients showed IIH, which was associated with shorter overall survival. On the basis of a triple-tracer PET approach, multiple phenotypic combinations were found. Correlation of these imaging phenotypes with genomics and treatment response will be relevant for precision medicine.

CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsy-proven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality.

Phase II multicenter trial combining nivolumab and radiosurgery for NSCLC and RCC brain metastases.

Background: Anti-PD-1 has activity in brain metastases (BM). This phase II open labeled non-randomized single arm trial examined the safety and efficacy of combining nivolumab with radiosurgery (SRS) in the treatment of patients with BM from non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Methods: This was a multicenter trial (NCT02978404) in which patients diagnosed with NSCLC or RCC, having ≤ 10 cc of un-irradiated BM and no prior immunotherapy were eligible. Nivolumab (240 mg or 480 mg IV) was administered for up to 2 years until progression. SRS (15-21 Gy) to all un-irradiated BM was delivered within 14 days after the first dose of nivolumab. The primary endpoint was intracranial progression free survival (iPFS). Results: Twenty-six patients (22 NSCLC and 4 RCC) were enrolled between August 2017 and January 2020. A median of 3 (1-9) BM were treated with SRS. Median follow-up was 16.0 months (0.43-25.9 months). Two patients developed nivolumab and SRS related grade 3 fatigue. One-year iPFS and OS were 45.2% (95% CI 29.3-69.6%) and 61.3% (95% CI 45.1-83.3%), respectively. Overall response (partial or complete) of SRS treated BM was attained in 14 out of the 20 patients with ≥1 evaluable follow-up MRI. Mean FACT-Br total scores were 90.2 at baseline and improved to 146.2 within 2-4 months (P = .0007). Conclusions: The adverse event profile and FACT-Br assessments suggested that SRS during nivolumab was well tolerated. Upfront SRS with the initiation of anti-PD-1 prolonged the 1-year iPFS and achieved high intracranial control. This combined approach merits validation randomized studies.

Testing Mayo Clinic's New 20/20/20 Risk Model in Another Cohort of Smoldering Myeloma Patients: A Retrospective Study.

Background-smoldering multiple myeloma (SMM) risk of progression to multiple myeloma (MM) is highly heterogeneous and several models have been suggested to predict this risk. Lakshman et al. recently proposed a model based on three biomarkers: bone marrow plasma cell (BMPC) percentage > 20%, free light chain ratio (FLCr) > 20 and serum M protein > 20 g/L. The goal of our study was to test this "20/20/20" model in our population and to determine if similar results could be obtained in another cohort of SMM patients. Method-we conducted a retrospective, single center study with 89 patients diagnosed with SMM between January 2008 and December 2019. Results-all three tested biomarkers were associated with an increased risk of progression: BMPC percentage ≥ 20% (hazard ratio [HR]: 4.28 [95%C.I., 1.90-9.61]; p < 0.001), serum M protein ≥ 20 g/L (HR: 4.20 [95%C.I., 1.90-15.53]; p = 0.032) and FLCr ≥ 20 (HR: 3.25 [95%C.I., 1.09-9.71]; p = 0.035). The estimated median time to progression (TTP) was not reached for the low and intermediate risk groups and was 29.1 months (95%C.I., 3.9-54.4) in the high-risk group (p = 0.006). Conclusions-the 20/20/20 risk stratification model adequately predicted progression in our population and is easy to use in various clinical settings.

Isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma according to prior lines of treatment and refractory status: ICARIA-MM subgroup analysis.

Patients with relapsed/refractory multiple myeloma (RRMM) experience several relapses, and become refractory to successive therapies. In the ICARIA-MM trial (NCT02990338), isatuximab plus pomalidomide-dexamethasone prolonged median progression-free survival (PFS) in patients with RRMM. This subgroup analysis of ICARIA-MM assessed the treatment benefit of isatuximab by prior lines of therapy and refractory status. A total of 307 patients were randomized to isatuximab-pomalidomide-dexamethasone (n = 154) or pomalidomide-dexamethasone (n = 153). Isatuximab (10 mg/kg intravenously) was given weekly in the first 28-day cycle, then every other week. Standard pomalidomide-dexamethasone doses were given. PFS was assessed by prior lines and refractory status. Overall, 102 (66 %) patients receiving isatuximab-pomalidomide-dexamethasone and 101 (66 %) patients receiving pomalidomide-dexamethasone had received 2-3 prior lines; 52 (34 %) and 52 (34 %) had received >3 prior lines, respectively. Median PFS was higher with isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone for patients who received 2-3 prior lines of therapy (12.3 vs. 7.8 months) and >3 prior lines of therapy (9.4 vs. 4.3 months). Median PFS was higher with isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone for patients who were lenalidomide-refractory (11.4 vs. 5.6 months), lenalidomide-refractory at last line (11.6 vs. 5.7 months), refractory to a proteasome inhibitor (PI) (11.4 vs. 5.6 months), and double-refractory (11.2 vs. 4.8 months). Overall response rate (ORR) in patients receiving isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone was 59.0 % versus 31.4 % in lenalidomide-refractory; 60.2 % versus 32.2 % in PI-refractory; and 58.6 % versus 29.9 % in double-refractory patients. Isatuximab-pomalidomide-dexamethasone improved PFS and ORR regardless of prior lines of therapy or refractory status, consistent with the benefit in the overall population.

Pomalidomide, bortezomib, and dexamethasone for multiple myeloma previously treated with lenalidomide (OPTIMISMM): outcomes by prior treatment at first relapse.

In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib, and dexamethasone (PVd) demonstrated superior efficacy vs bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma previously treated with lenalidomide, including those refractory to lenalidomide. This analysis evaluated outcomes in patients at first relapse (N = 226) by lenalidomide-refractory status, prior bortezomib exposure, and prior stem cell transplant (SCT). Second-line PVd significantly improved PFS vs Vd in lenalidomide-refractory (17.8 vs 9.5 months; P = 0.0276) and lenalidomide-nonrefractory patients (22.0 vs 12.0 months; P = 0.0491), patients with prior bortezomib (17.8 vs 12.0 months; P = 0.0068), and patients with (22.0 vs 13.8 months; P = 0.0241) or without (16.5 vs 9.5 months; P = 0.0454) prior SCT. In patients without prior bortezomib, median PFS was 20.7 vs 9.5 months (P = 0.1055). Significant improvement in overall response rate was also observed with PVd vs Vd in lenalidomide-refractory (85.9% vs 50.8%; P < 0.001) and lenalidomide-nonrefractory (95.7% vs 60.0%; P < 0.001) patients, with similar results regardless of prior bortezomib or SCT. No new safety signals were observed. These data demonstrate the benefit of PVd at first relapse, including immediately after upfront lenalidomide treatment failure and other common first-line treatments.

Sarcoidosis and Cancer: A Complex Relationship.

Sarcoidosis is a systemic disease of unknown etiology, characterized by the presence of non-caseating granulomas in various organs, mainly the lungs, and the lymphatic system. Since the individualization of sarcoidosis-lymphoma association by Brincker et al., the relationship between sarcoidosis or granulomatous syndromes and malignancies has been clarified through observational studies worldwide. Two recent meta-analyses showed an increased risk of neoplasia in sarcoidosis. The granulomatosis can also reveal malignancy, either solid or hematological, defining paraneoplastic sarcoidosis. Recent cancer immunotherapies, including immune checkpoint inhibitors (targeting PD-1, PD-L1, or CTLA-4) and BRAF or MEK inhibitors were also reported as possible inducers of sarcoidosis-like reactions. Sarcoidosis and neoplasia, especially lymphoma, can show overlapping presentations, thus making the diagnosis and treatment harder to deal with. There are currently no formal recommendations to guide the differential diagnosis workup between the evolution of lymphoma or a solid cancer and a granulomatous reaction associated with neoplasia. Thus, in atypical presentations (e.g., deeply impaired condition, compressive lymphadenopathy, atypical localization, unexplained worsening lymphadenopathy, or splenomegaly), and treatment-resistant disease, targeted biopsies on suspect localizations with histological examination could help the clinician to differentiate neoplasia from sarcoidosis. Pathological diagnosis could sometimes be challenging since very few tumor cells may be surrounded by massive granulomatous reaction. The sensitization of currently available diagnostic tools should improve the diagnostic accuracy, such as the use of more "cancer-specific" radioactive tracers coupled with Positron Emission Tomography scan.