Response rates of extra-nodal diffuse large B cell lymphoma to anti-CD19-CAR T cells: A real word retrospective multicenter study.

Chimeric antigen receptor T-cells (CAR-T) are widely used for the treatment of relapsed/refractory diffuse large B cell lymphoma (DLBCL). The data for CAR-T cell therapy in patients with extra-nodal (EN) lymphoma is restricted. We included 126 consecutive patients with DLBCL treated with commercially available CAR-T cells (tisagenlecleucel, n = 100, 79.4% and axicabtagene ciloleucel, n = 26, 20.6%). At lymphodepletion, 72 of 126 (57%) patients had EN disease, 42 of 126 (33%) patients had nodal disease (ND)-only and 12 of 126 (10%) showed no disease assessed by PET-CT. There were no significant differences in CAR-T related toxicities and in the median Progression free survival (PFS) between EN patients and ND (10.76 [95% CI: 7.8-13.6] vs. 14.1 [95% CI: 10-18.1] months, p = .126). Similarly, median overall survival (OS) was not significantly different (15.36 [95% CI 12.5-18.2] vs. 18.4 [95% CI 14.8-22.1] months, p = .100). Subgroup analysis according to the number of EN involved sites showed that median PFS and OS were significantly higher in patients with <3 EN sites (12.3 months [95% CI 9-15.5] vs. 4.28 months [95% CI 0.6-7.9], p = .010) compared to patients with >2 EN sites, respectively (16.5 months [95% CI 13.4-19.6] vs. 8.7 months [95% CI 4.6-12.8], p = .05). In multivariate cox regression analysis, increased number sites of EN disease and high lactate dehydrogenase (LDH) at lymphodepletion negatively impacted PFS (p = .021 and <.001, respectively), while sex, type of product administered, age and performance status did not predict PFS and OS. Of note, all the patients with involvement of gastrointestinal tract (n = 9), urinary tract (n = 9), or pharynx (n = 3) at lymphodepletion, progressed or had an early relapse. In conclusions, patients with >2 EN sites at lymphodepletion have significantly worse clinical outcomes compared to patients with <3 EN sites. Patients with specific sites of EN disease may demonstrate grim prognosis.

Polatuzumab-based regimen or CAR T cell for patients with refractory/relapsed DLBCL-a matched cohort analysis.

Polatuzumab (Pola)-based regimens and chimeric antigen receptor T (CAR T) cells provide superior outcome compared to conventional chemoimmunotherapy in patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL). Choosing between these strategies remains controversial. The efficacy of CAR T versus Pola-rituximab(R) /Pola-bendamustine(B)-R in R/R DLBCL patients after failing ≥2 lines of treatment was compared in a retrospective, 'real-world' study. Propensity score matching, for age, lymphoma category (de-novo/transformed), number of prior lines, Eastern Cooperative Oncology Group performance status and lactate dehydrogenase level, was applied to control for differences in patients' characteristics. Response rate, progression-free survival (PFS) and overall survival (OS) were analyzed. A total of 82 patients, treated with CAR T (n=41) or Pola-based regimens (n=41), were included. No treatment-related deaths occurred with CAR T vs. 3 (7.3%) with Pola. The overall and complete response rates were 83% and 58% with CAR T vs. 66% and 44% with Pola-based-regimens (p=0.077 and p=0.18, respectively). At a median follow-up of 9 months (range 1-19.2) and 16 months (range 0.7-25.3) for the CAR T and Pola arm respectively, the median PFS has not been reached for CAR T vs. 5.6 months for Pola (95% CI 3.6-7.6, p=0.014). Median OS has not been reached for CAR T vs. 10.8 months (95% CI 2.2-19.4) for Pola (p=0.026). To conclude, in a real-world setting, treatment with CAR T achieved superior PFS and OS compared to Pola-based regimens in patients with R/R DLBCL.

Characteristics and recognition of early infections in patients treated with commercial anti-CD19 CAR-T cells.

The characteristics of infections following chimeric antigen receptor T (CAR-T) cells targeting CD19 in real-word population are obscure. We analyzed infections' characteristics in the first month among consecutive patients with diffuse large B-cell lymphoma (DLBCL) (n = 60, median age, 69.3 years), treated with commercial CAR-T cells. ECOG performance status (PS) was 2-3 in most patients (58%). Infections were observed in 45% of patients (16, 27%, bacterial infections, and 14, 23%, viral infections). Bacterial infection included clinically documented infection in 7 (Pneumonia, n = 5; periodontal infection, n = 1; and cellulitis, n = 1) and microbiology documented infection (MDI) in 9 patients (Gram-negative rod, n = 5; Gram-positive cocci, n = 3, bacteremia; polymicrobial, n = 1). The most common viral infection was cytomegalovirus (CMV) reactivation (n = 10, 17%) leading to initiation of anti-CMV treatment in 6 (60%) among these patients. None had CMV disease. In univariate analysis, immune effector cell-associated neurotoxicity syndrome (ICANS) was associated with higher incidence of bacterial infection (OR=4.5, P = .018), while there was a trend for lower incidence of bacterial infections in patients with chemosensitive disease to bridging therapy (OR=0.375, P = .074). Age or PS was not associated with increased risk of bacterial infection. Increase in C-reactive protein (CRP) prior to fever onset was associated with microbiologically documented infections. We conclude that infections are common in the first month following CAR-T-cell administration, however, were not increased in elderly patients or those presenting with poorer PS. Increase in CRP prior to fever onset could support infection over cytokine release syndrome.

Humoral response rate and predictors of response to BNT162b2 mRNA COVID19 vaccine in patients with multiple myeloma.

Multiple myeloma (MM) patients are at excess risk for clinically significant COVID19 infection. BNT162b2 mRNA COVID19 (BNT162b2) vaccine provides effective protection against COVID19 for the general population, yet its effect in MM patients may be compromised due to disease and therapy-related factors and was not yet evaluated. This single-centre prospective study included MM patients tested for serological response 14-21 days post second vaccine. Vaccinated healthy volunteers served as controls. In all, 171 MM patients, median age 70 (38-94) were included; 159 active MM and 12 smouldering myeloma (SMM). Seropositive response rate (median titer) was 76% (91 U/ml) in active MM patients vs 98% (992 U/ml) in the 64 controls (P < 0·0001), and 100% (822 U/ml) in SMM patients. Multivariate analysis revealed older age (P = 0·009), exposure to ≥4 novel anti-myeloma drugs (P = 0·02) and hypogammaglobulinaemia (P = 0·002) were associated with lower response rates. None of the novel agents significantly decreased response rate, whereas daratumumab trended towards reduced response (P = 0·08). Adverse events occurred in 53% and 55% of the MM patients and controls, respectively, all transient grade 1-2. In conclusion, BNT162b2 vaccine was safe and provided a high seropositivity rate in MM patients, independent of treatment type. Older, hypogammaglobulinaemic and heavily pretreated patients had lower response rates.

Newly diagnosed multiple myeloma patients carrying monoallelic deletion of the whole locus of immunoglobulin heavy chain gene have a better prognosis compared to those with t(4;14) and t(14;16).

The current study evaluated the prognostic significance of the monoallelic deletion of the whole locus of the immunoglobulin heavy-chain (w_del(IGH)) gene compared to translocations t(4;14) and t(14;16) among newly diagnosed multiple myeloma (MM) patients. We retrospectively analyzed clinical (age, gender, and staging) and laboratory data at diagnosis and the overall survival (OS) of 255 newly diagnosed MM patients carrying w_del(IGH) or translocations t(4;14) or t(14;16). Bone marrow samples were examined by morphological and sequential interphase fluorescense in situ hybridization analyses. Among 255 patients, 117 (45.8%) had w_del(IGH), 99 (38.8%) had t(4;14), and 39 (15.3%) had t(14;16). Mean age was 61.6 ± 11.6 years. Groups did not differ significantly in age, gender, or lactate dehydrogenase levels. Patients in the w_del(IGH) group presented more frequently at International Staging System stage I than at stage II/III. Patients in the w_del(IGH) group had significantly fewer additional chromosomal aberrations (1.58) than the other two groups (2.3 and 2.13 in the del(IGH), t(14;16) and t(4;14) groups, respectively, P < 0.0001). Furthermore, the w_del(IGH) group had significantly longer estimated median OS (9.47 years) compared to those with translocations t(14;16) (3.02 years, P = 0.002) or t(4;14) (4.18 years, P = 0.001), respectively. These findings suggest a potential prognostic significance of monoallelic deletion of IGH among these patients. Additional studies are needed to better understand the nature and mechanism of this prognostic factor.

Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Single-Group, Phase 2, Open-Label Study.

Background: Treatment-free remission (TFR)-that is, stopping tyrosine kinase inhibitor (TKI) therapy without loss of response-is an emerging treatment goal in chronic myeloid leukemia (CML). Objective: To evaluate TFR after discontinuation of second-line nilotinib therapy. Design: Single-group, phase 2, open-label study. (ClinicalTrials.gov: NCT01698905). Setting: 63 centers in 18 countries. Patients: Adults with CML in chronic phase who received TKI therapy for at least 3 years (>4 weeks with imatinib, then ≥2 years with nilotinib) and achieved MR4.5 (BCR-ABL1 ≤0.0032% on the International Scale [BCR-ABL1IS]) while receiving nilotinib entered a 1-year consolidation phase. Those with sustained MR4.5 during consolidation were eligible to enter TFR. Interventions: Patients received nilotinib during consolidation; those who entered TFR stopped treatment. Patients with loss of major molecular response (MMR) (BCR-ABL1IS ≤0.1%) or confirmed loss of MR4 (BCR-ABL1IS ≤0.01%) during TFR reinitiated nilotinib treatment. Measurements: Proportion of patients without loss of MMR, confirmed loss of MR4, or treatment reinitiation within 48 weeks of stopping treatment (primary end point). Results: 163 patients who had switched from imatinib to nilotinib (for reasons including resistance, intolerance, and physician preference) enrolled in the study and entered the consolidation phase. Of these patients, 126 met the criteria for entering the TFR phase, and 73 (58% [95% CI, 49% to 67%]) and 67 (53% [CI, 44% to 62%]) maintained TFR at 48 weeks (primary end point) and 96 weeks, respectively. Of the 56 patients who reinitiated nilotinib therapy, 55 regained MMR or better and 52 regained MR4.5. None had CML progression to accelerated phase or blast crisis. Musculoskeletal pain was more frequent during the first 48 weeks after nilotinib discontinuation. Limitation: The study included a heterogeneous patient population and was not designed to compare outcomes between patients continuing and those stopping treatment. Conclusion: TFR seems achievable in patients with sustained MR4.5 after switching to nilotinib. Primary Funding Source: Novartis Pharmaceuticals Corporation.

Severe cytomegalovirus enterocolitis developing following daratumumab exposure in three patients with multiple myeloma.

OBJECTIVES: The risk of cytomegalovirus (CMV) reactivation in multiple myeloma (MM) patients treated with bortezomib-based induction regimens is increased following autologous stem cell transplantation (ASCT). There is paucity of data regarding the risk of CMV infections in MM patients who did not receive bortezomib and ASCT. METHODS: We herein report three cases of heavily pretreated MM patients, receiving daratumumab-containing combination regimens, in whom ASCT had been performed long ago and who recently developed severe CMV-related gastrointestinal disease. RESULTS: All the three patients had a prolonged CMV disease course requiring a long-term antiviral treatment. All the patients suffered from CMV colitis. One patient had concurrent CMV duodenitis and another patient had a concurrent CMV retinitis. CONCLUSION: Novel myeloma treatments prolong patient survival and more patients with profound immunosuppression following multiple lines of therapies are seen in clinical practice. These patients may present with opportunistic infections that were rare in the past. Our findings suggest a possible association between daratumumab therapy (in combination with other immunosuppressive therapies) and severe CMV gastrointestinal disease. A longer follow-up is needed to explore long-term side effects of novel agents like daratumumab in newly diagnosed as well as heavily pretreated MM patients.

Serum free immunoglobulin light chain fingerprint identifies a subset of newly diagnosed multiple myeloma patients with worse outcome.

Multiple myeloma (MM) is a multi-subclonal malignancy with relatively high heterogeneity. Patients who initially presented with both monoclonal-protein (MP) and free light chain (FLC) secretion but then relapsed with a light chain escape pattern have been shown to reflect disease clonal evolution and to bare a worse prognosis. We hypothesized that a discordant MP/FLC pattern at diagnosis may reflect a similar clonal evolution that had occurred prior to diagnosis of active myeloma, conferring a worse outcome. We analyzed 255 consecutive newly diagnosed MM patients who received first line bortezomib-based therapy between 2007 and 2014, hypothesizing that their MP/FLC fingerprint at diagnosis reflects clonal heterogeneity and, therefore, affects outcome. An involved FLC level ≥ 700 mg/L and MP ≥ 2.5 g/L were used as cutoffs for low vs high FLC and MP levels, respectively. Patients were divided into 4 subgroups according to their involved FLC and MP blood levels at diagnosis: HiLC and HiMP for patients with either a predominant FLC or a predominant MP, respectively, and HiLC-MP and LoLC-MP when both FLC and MP were increased or decreased, respectively. There were 68 (27%) patients with HiLC, which presented more often with International Staging System-3 stage (P < .0001). Multivariate analysis showed that HiLC was associated with a 5.1-fold risk for mortality in a multivariate model (95% confidence interval [CI], 1.34-19.68). Both HiLC and HiLC-MP phenotypes were associated with shorter progression-free survival (hazard ratio of 2.66 [95% CI, 1.33-5.32] and 2.82 [95% CI, 1.37-5.83], respectively), independently of other prognostic factors, including the use of autograft. Thus, we identified an LC predominant secretory fingerprint (HiLC phenotype) at diagnosis as a potential independent risk factor that may affect disease control and survival in newly diagnosed MM patients treated with bortezomib-based induction therapy; this may represent increased subclonal heterogeneity.

Comparison of engraftment following different stem cell mobilization modalities in patients with multiple myeloma treated with a uniform induction regimen containing bortezomib, cyclophosphamide and dexamethasone.

Bortezomib-based induction followed by autologous stem cell transplantation is a common treatment for multiple myeloma (MM). Stem cell (SC) mobilization with granulocyte-colony stimulating factor (G-CSF) alone has become an alternative to G-CSF combined with chemotherapeutic agents. This study aimed to compare the efficacy of the two mobilization modalities following induction with a uniform regimen containing bortezomib, cyclophosphamide and dexamethasone (VCD). We retrospectively evaluated results of SC mobilization using either G-CSF alone or combined with high-dose cyclophosphamide (HD-CY) in MM patients after VCD induction. The primary endpoints of the study were engraftment and mobilization-associated toxicity. Parameters of stem cell collection, transplantation and engraftment were assessed. Data of 92 patients were analyzed [56 (61%) mobilized with HD-CY + G-CSF and 36 (39%) with G-CSF only]. HD-CY + G-CSF provided a higher number of CD34 + cells (15.9 vs 8.1 × 106/kg, p = 0.001) with fewer apheresis sessions. However, while no adverse events were observed in patients receiving G-CSF alone, nine patients (16%) receiving HD-CY + G-CSF developed neutropenic fever requiring hospitalization. Although a greater number of cells was transplanted following mobilization with HD-CY + G-CSF, neutrophil and platelet engraftment and duration of transplant-related hospitalization were similar in both cohorts. G-CSF alone provided a sufficient SC amount, without exposing patients to additional toxicity. While HD-CY + G-CSF resulted in a superior SC yield in MM patients induced with VCD, this advantage should be balanced against adverse effects of this mobilization regimen.

Progressive refractory light chain amyloidosis and multiple myeloma patients are responsive to the addition of clarithromycin to IMiD based therapy.

Multiple myeloma (MM) and primary systemic light chain amyloidosis (AL) are both chronic plasma cell dyscrasias with different clinical expression but limited treatment options for relapsed refractory disease. We report the effect of the addition of clarithromycin on 31 MM and 17 AL with relapsed or refractory disease who had an insufficient response or disease progression while on an IMiD based therapy. In this high risk population, hematological response was reported in 48% of MM patients and 94% of AL patients. Responses were reported early in both groups (median 35 days) and were more sustained in AL patients. Adverse events were common and included mostly grade 1-2 fatigue, infections and abdominal discomfort. Cytopenias were common and cardiac complications were rare in both MM and AL patients. Clarithromycin-IMiD combination therapy appears to be both effective and safe in progressive MM and primarily in AL patients, although a prospective clinical trial is warranted to validate these results. Am. J. Hematol. 92:131-135, 2017. © 2016 Wiley Periodicals, Inc.

Translocation t(11;14) in newly diagnosed patients with multiple myeloma: Is it always favorable?

The most common translocation in multiple myeloma (MM) is t(11;14)(q13;q32). According to several studies, this translocation represents a unique subset of patients with relatively favorable outcomes. Using combined analyses of morphology and fluorescence in situ hybridization (I-FISH), we examined the co-occurrence rates of t(11;14) with seven chromosomal aberrations (CAs), del(13q), del(17p), del(1p), gain(1q), multiple gains(1q), del(16q), and del(IGH), and assessed the effect of the different combinations on patient outcomes, with overall survival (OS) as the main outcome measure. Bone marrow samples and clinical data from 212 patients with MM with t(11;14) were analyzed. At least two additional CAs were found in 35% (75/205) of patients and a strong correlation between specific CAs. The occurrence of three CAs [multiple gains of (1q) (HR = 6.94, P = 0.001), del(1p) (HR = 4.47, P = 0.008), and del(IGH) (HR = 2.38, P = 0.002)] exerted a profoundly deleterious effect on median OS when compared with patients with t(11;14) only. Del(17p) and del(13q) have also exerted a deleterious effect albeit to a lesser extent (HR = 2.05, P = 0.07 and HR = 1.81, P = 0.03, respectively). When compared with t(11;14) alone, the addition of certain CAs lead to worse outcomes. These findings may have important clinical and biological implications. Patients with coexisting adverse lesions and t(11;14) may be considered at high risk and managed accordingly. © 2016 Wiley Periodicals, Inc.

[HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE PERSPECTIVE OF TIME AND UP TO THE 2000 TRANSPLANT AT THE RAMBAM HEALTH CARE CAMPUS].

INTRODUCTION: Stem cell transplantation is indicated in hematological malignancies as well as some solid tumors and congenital abnormalities. Autologous transplantation allows the administration of high dose chemotherapy without prolonged bone marrow aplasia. Allogeneic transplantation allows us to give the patient a new immune system that can locate and destroy remaining tumor cells. First attempts in patients began in 1939. Improved outcomes occurred after discovering the human leukocyte antigen system which allowed for matching the donor to the patient. Immunosuppression therapy to prevent graft versus host disease also improved the outcomes. Since the 1970's, more and more centers in North America and Europe opened stem cell transplantation programs. Today it is performed worldwide and on December 2012, the one million milestone transplant worldwide was achieved. The bone marrow transplantation program started at Rambam Health Care campus on September 1995. Since then 2000 transplantations were performed at Rambam. A third of these procedures were allogeneic and two thirds were autologous. In the last decade patient survival has improved significantly due to better supportive care and the use of reduced intensity conditioning relying on the graft versus tumor effect (GVT). New ways to reduce graft versus host disease (GVHD), while improving GVT effect are based on manipulating T cells in the graft and on genetically engineered T cell with enhanced antitumor cytotoxicity. In the future, allogeneic transplantation will become more complex, more individualized and more efficient.

Integration of CT-Based Measurements into Surveillance PET/CT in Patients with Diffuse Large B Cell Lymphoma.

BACKGROUND: Despite the lack of clinical studies supporting the use of routine surveillance FDG-positron emission tomography (PET) in patients with diffuse large B cell lymphoma (DLBCL) who achieved remission, many centers still use this strategy, especially in high risk patients. Surveillance FDG-PET computed tomography (CT) is associated with a high false positive (FP) rate in DLBCL patients. OBJECTIVES: To investigate whether use of specific CT measurements could improve the positive predictive value (PPV) of surveillance FDG-PET/CT. METHODS: This retrospective study included DLBCL patients treated with CHOP or R-CHOP who achieved complete remission and had at least one positive surveillance PET. CT-derived features of PET-positive sites, including long and short diameters and presence of calcification and fatty hilum within lymph nodes, were assessed. Relapse was confirmed by biopsy or consecutive imaging. The FP rate and PPV of surveillance PET evaluated with/without CT-derived measurements were compared. RESULTS: Seventy surveillance FDG-PET/CT scans performed in 53 patients were interpreted as positive for relapse. Of these studies 25 (36%) were defined as true-positive (TP) and 45 (64%) as FP. Multivariate analysis found long or short axis measuring ≥ 1.5 and ≥ 1.0 cm, respectively, in PET-positive sites, International Prognostic Index (IPI) ≥ 2, lack of prior rituximab therapy and FDG uptake in a previously involved site, to be independent predictors of true positive surveillance PET (odds ratio 5.4, 6.89, 6.6, 4.9, P < 0.05 for all). CONCLUSIONS: PPV of surveillance PET/CT may be improved by its use in selected high risk DLBCL patients and combined assessment of PET and CT findings.

Monocyte count at diagnosis is a prognostic parameter in diffuse large B-cell lymphoma: results from a large multicenter study involving 1191 patients in the pre- and post-rituximab era.

In this study we assessed the prognostic significance of absolute monocyte count and selected the best cut-off value at diagnosis in a large cohort of patients with diffuse large B-cell lymphoma. Data were retrieved for therapy-naïve patients with diffuse large B-cell lymphoma followed in Israel and Italy during 1993-2010. A final cohort of 1017 patients was analyzed with a median follow up of 48 months and a 5-year overall survival rate of 68%. The best absolute monocyte count cut-off level was 630/mm(3) and the 5-year overall survival for patients with counts below this cut-off was 71%, whereas it was 59% for those with a count >630 mm(3) (P=0.0002). Of the 1017 patients, 521 (51%) were treated with chemo-immunotherapy, and in this cohort, using multivariate analysis, elevated monocyte count retained a negative prognostic value even when adjusted for International Prognostic Index (HR1.54, P=0.009). This large study shows that a simple parameter such as absolute monocyte count (>630/mm(3)) can easily be used routinely in the evaluation of newly diagnosed diffuse large B-cell lymphoma to identify high-risk patients with a worse survival in the rituximab era.

Reproductive organ involvement in non-Hodgkin lymphoma during pregnancy: a systematic review.

Data for pregnancy-associated non-Hodgkin lymphoma are limited to case reports, making it difficult to define this disorder. We did a systematic search for articles published between 1967 and 2011 with the aim to determine the characteristics, management, and outcome of pregnancy-associated non-Hodgkin lymphoma. We identified 121 patients from 74 papers. Most patients with stage information available presented with stage IV disease (75%, 82 of 108 patients). Patients were classified into three clinical groups; those with indolent lymphomas accounted for 5% (five of 108), aggressive lymphomas (diffuse large B-cell lymphoma and T-cell lymphomas) made up 48% of patients (52 of 108), and highly aggressive lymphomas (Burkitt's lymphoma, immunoblastic lymphoma, and unspecified highly aggressive lymphomas) accounted for 47% of patients (51 of 108). Reproductive organ involvement (breast, ovary, uterus, placenta) was reported in 49% of 110 patients with information available on extranodal involvement, and prevailed in endemic Burkitt's lymphoma (100%, 19 of 19), followed by non-endemic Burkitt lymphoma (70%, 14 of 20), immunoblastic lymphoma (67%, two of three), peripheral T-cell lymphoma (46%, six of 13), and indolent (40%, two of five) and diffuse large cell lymphoma (23%, nine of 40). Most patients received antepartum (45%, 55 of 121) or postpartum therapy (45%, 54 of 121), resulting in 6-month survival of 53% for mothers and a livebirth rate of 83%. Pregnancy-associated non-Hodgkin lymphoma has unique clinical characteristics with frequent reproductive organ involvement. Collaborative prospective studies are needed to further characterise pathophysiological and clinical aspects of this complication.

Lower Patient Anxiety and Unchanged Levels of Adherence to Hemato-Oncologic Treatment in Response to New Measures to Reduce Hospital Exposure Risk to COVID-19.

OBJECTIVE: Hemato-oncology patients are at high risk for morbidity and mortality from coronavirus disease (COVID-19). The resultant heightened anxiety among these patients may negatively affect adherence to therapy and treatment-related outcome. We aimed to assess whether the adoption of precautionary measures provided by the medical team led to a reduction in COVID-19-related anxiety and, consequently, to successful execution of treatment plans. METHODS: All adult hemato-oncology patients actively treated or being followed-up at the outpatient service at Tel Aviv Sourasky Medical Center between March 25 and May 3, 2020, were invited to answer a questionnaire that focused on their anxiety and adherence to treatment following new measures to reduce risk of infection during the first COVID-19 outbreak. RESULTS: One hundred and fifty patients (representing 24% of those being approached), average age 67 years, 52% male, and 57% undergoing antineoplastic therapy, responded to the survey. The introduction of precautionary measures resulted in a significant reduction in anxiety level in all patients, irrespective of age, sex, or treatment status. Attendance to scheduled visits in day care and outpatient clinics remained unchanged. Adherence to planned blood and imaging tests were 81% and 73%, respectively, and 93% of the patients were satisfied with their medical care. Thirty-two percent of patients used telemedicine. Satisfaction with telemedicine was highest among non-actively treated patients and those experiencing high anxiety levels. CONCLUSION: Reorganization of the hemato-oncology unit and provision of information to patients reduced COVID-19-related anxiety and enabled the same delivery of therapy as that prior to the pandemic.

Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study.

BACKGROUND: Daratumumab (Dara) is generally well tolerated, but is associated with increased risk of infection. METHODS: We investigated hypogammaglobinemia occurrence in different Dara-based regimens. Multiple myeloma (MM) patients were treated with ⩾2 cycles of Dara-based therapy during 2016-2020, mainly for relapsed/refractory disease. Data on patient characteristics, treatment regimens, polyclonal IgG (poly-IgG) and uninvolved free light chain (Un-FLC) levels during treatment, as well as predictors for hypogammaglobinemia and predictors for infections, were evaluated retrospectively. RESULTS: A total of 84 patients, median age 67.2 years, were included. Dara, mainly as ⩾2 line therapy (88.1%, n = 74), was combined with immunomodulating drugs (IMiDs) (53%), proteasome inhibitors (PIs) (15%), IMiDs-PIs (11%), or dexamethasone only (21%). Median treatment duration was 13 months. Median Poly-IgG levels at 0, 2, and 4 months were 7.1 g/l, 4.5 g/l, and 4 g/l, respectively, and remained low throughout treatment. Lower poly-IgG pre-Dara (p = 0.001) and Dara-PIs (±IMiDs) regimen were associated with lower poly-IgG levels at 4 months (p = 0.03). Only patients treated with Dara monotherapy had partial immune reconstitution, reflected by resumption of IgM levels. Most (85%) patients developed ⩾1 infections, mostly grade 1-2 respiratory (76%). A lower poly-IgG level post Dara (RR = 1.137 p = 0.026) predicted increased risk of any infection. Intravenous immunoglobulin (IVIG) was associated with a significant decrease in all infections. CONCLUSION: Relapsed MM patients treated with Dara, often experience persistent hypogammaglobinemia, irrespective of responsiveness to treatment. Infections, especially respiratory, are frequent and apparently related to low Poly-IgG levels. IVIG should be considered for reducing infections in these patients.

Characteristics and outcome of multiple myeloma patients presenting with anaemia only: A retrospective multi-centre study.

BACKGROUND: Multiple myeloma (MM) patients presenting with anaemia as their sole clinical manifestation are rare and not fully defined. METHODS: Retrospective multi-site study comparing the characteristics and outcome of MM patients with anaemia only with matched patients, presenting with multi-organ disease. RESULTS: Anaemia-only patients had a higher percentage of bone marrow monoclonal plasma cells group (median 60% [IQR 42-80%] vs. 37% [IQR 17-65%], respectively; p < 0.001), and a lower responsiveness to treatment (≥VGPR rates were 54% vs 74%, p = 0.049). Median survival in anaemia only patients was 65.9 ± 6.9 vs 83.4 ± 8.8 months in matched control patients (P = n.s). CONCLUSIONS: MM patients presenting with anaemia only represents a unique, potentially less favorable population.

Safety and Immunogenicity of the BNT162b2 mRNA COVID-19 Vaccine in Patients after Allogeneic HCT or CD19-based CART therapy-A Single-Center Prospective Cohort Study.

Data are scarce regarding both the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing immune cell therapy; thus, we prospectively evaluated these two domains in patients receiving this vaccine after allogeneic hematopoietic cell transplantation (HCT; n = 66) or after CD19-based chimeric antigen receptor T cell (CART) therapy (n = 14). Overall, the vaccine was well tolerated, with mild non-hematologic vaccine-reported adverse events in a minority of the patients. Twelve percent of the patients after the first dose and 10% of the patients after the second dose developed cytopenia, and there were three cases of graft-versus-host disease exacerbation after each dose. A single case of impending graft rejection was summarized as possibly related. Evaluation of immunogenicity showed that 57% of patients after CART infusion and 75% patients after allogeneic HCT had evidence of humoral and/or cellular response to the vaccine. The Cox regression model indicated that longer time from infusion of cells, female sex, and higher CD19+ cells were associated with a positive humoral response, whereas a higher CD4+/CD8+ ratio was correlated with a positive cellular response, as confirmed by the ELISpot test. We conclude that the BNT162b2 mRNA COVID-19 vaccine has impressive immunogenicity in patients after allogeneic HCT or CART. Adverse events were mostly mild and transient, but some significant hematologic events were observed; hence, patients should be closely monitored.