Abstract
This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated ...with anti-Spike (S) IgG d42 titers (Spearman r = 0.865,
p
< 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (
p
< 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19
+
B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026,
p
= 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.
The feasibility and efficacy of high-dose melphalan followed by autologous hematopoietic stem cell transplantation in newly diagnosed elderly patients with multiple myeloma was analyzed ...prospectively. Fifty-six multiple myeloma patients, aged 65 years or over, from 6 French centers were studied. The induction therapy was bortezomib-based in combination with dexamethasone and either thalidomide, cyclophosphamide or lenalidomide, for 4-6 cycles. Peripheral blood stem cells were collected after high-dose cyclophosphamide plus G-CSF or G-CSF alone, with plerixafor if needed. The conditioning regimen consisted of melphalan at 140 mg/m
in 18 patients (36%) and 200 mg/m
in 32 (64%). Three months post autologous hematopoietic stem cell transplantation, a 2-month consolidation phase with either lenalidomide plus dexamethasone or bortezomib-based combination therapy was allowed, but maintenance treatment was not given. All but 6 patients underwent autologous hematopoietic stem cell transplantation and 3 had tandem transplantations. The treatment-related mortality was 0% at 100 days post transplantation. Sixty-eight percent received consolidation therapy following transplantation. The best response achieved was 40% complete response, 36% very good partial response, and 18% partial response. After a median follow up of 21 months (range 6-31), the estimated progression-free and overall survival rates at two years were 76% 95%CI: (61.6-94.1) and 88% 95%CI: (76.7-100), respectively. The higher dose of melphalan (200 mg/m
) afforded superior progression-free and overall survival rates. This prospective study provides evidence for the safety and efficacy of autologous hematopoietic stem cell transplantation as a first-line treatment approach in elderly multiple myeloma patients. (clinicaltrials.gov identifier: 01671826).
Coexisting malignancies is not only an uncommon event but, it can also represent a medical challenge. Its complexity relies on the difficulty of management and the need for personalized and ...prioritized therapeutic approaches, on the one hand, and in the potential misdiagnosis of recurrence or even a de novo disease, on the other.
Here, we present a case of a 69-year-old patient, who was initially diagnosed with a chronic myelomonocytic leukemia (CMML), followed by monoclonal gammopathy of uncertain significance (MGUS). Few years later, the patient developed Hodgkin's lymphoma (HL), and a new mutation, previously undocumented in the medical literature, was also detected.
As a conclusion, we can say that the decision must be taken with caution and must be based on two major factors: 1- The rapid evolution of malignancies: give priority to treating the most rapid/life-threatening disease. 2- Prioritize the treatment of symptomatic disease and/or that which may most improve patients’ quality of life.
Induction with lenalidomide, bortezomib and dexamethasone (VRD) is a standard of care for newly diagnosed multiple myeloma patients (NDMM). However, lenalidomide might be difficult to manage, for ...example if acute kidney failure or thromboembolic events are present at diagnosis. In these cases, induction with bortezomib, cyclophosphamide and dexamethasone (VCD), might be more easily manageable. We conducted a retrospective study to assess efficacy of VCD and VRD as induction regimens, in NDMM, eligible for intensive treatment, treated between 2010 and 2020. Overall, 110 patients were treated, 62 received VCD and 48 VRD. Median age was 64 (range, 36-72) years in the VCD group and 59 (33-71) in the VRD group. There was no difference in ISS stage III status VCD n=21 (34%) vs VRD n=17 (35%), p=.5470, although there were more high-risk cytogenetics patients in the VRD group VCD n=4 (7%) vs VRD n=10 (16%), p=.248. Patients received a median number of 4 (3-9) cycles of VCD and 4 (3-8) cycles of VRD. Of note, in the VCD group, 5 (8%) patients switched to VRD, mostly because of renal function improvement. All patients completed the induction phase and underwent high dose melphalan (HDM) at 200 mg/m2: VCD, n=24 and VRD, n=40; or 140 mg/m2: VCD, n=37 and VRD, n=8, and autologous stem cell transplant (ACST). After ACST, 45 (63%) and 32 (67%) patients received consolidation treatment; 9 patients in the VCD group received VRD as consolidation. Among the 5 patients who switched from VCD to VRD, 1 also received VRD consolidation, 1 received RD without bortezomib, and 3 did not received consolidation. Then, 20 (32%) and 34 (71%) received maintenance with lenalidomide in the VCD and VRD group, respectively. Median follow-up was 3.75 years. Overall response rate (ORR) was similar in the two groups, whatever the time point: 98 vs 98% ORR was seen before HDM and ACST, 100 vs 98% after 3 months, 92 vs 93% after 6 months and 73 vs 73% after 1 year, for VCD and VRD groups, respectively. However, faster and deeper responses were achieved with VRD compared to VCD, with VGPR or more achieved in 79 vs 60% patients before ACST, 90 vs 77% after 3 months, 85 vs 77% after 6 months and 73 vs 65% after 1 year, respectively. There were no significant differences in survival data between groups. Progression-free survival was 3.2 years in the VCD group and 4.75 years in the VRD group (p=ns). Overall survival was not reached in the VCD group and 8.9 years in the VRD group (p=ns).
VRD yielded faster and deeper responses compared to VCD in our series, but this did not translate into significant differences of PFS nor OS. Even if VRD remains the standard induction regimen today for NDMM eligible for ACST, VCD remains a good alternative to VRD, with similar ORR and no significant differences in survival. We believe that these data are relevant and useful for clinicians who deal with multiple myeloma patients in daily practice. Multivariate analysis will be updated for IMW congress.
Summary
Lenalidomide maintenance in myeloma is well established. Nevertheless, pomalidomide could provide an alternative. Myeloma patients in first relapse, initially treated in the Intergroupe ...Francophone du Myélome (IFM) 2009 trial, and subsequently in the IFM 2013‐01 phase 2 trial, received four cycles of salvage therapy with pomalidomide plus cyclophosphamide plus dexamethasone (PCD) with transplantation plus 2 PCD consolidation or without transplantation but with 5 PCD and for all patients pomalidomide plus dexamethasone maintenance therapy. This consisted of 28‐day cycles of pomalidomide 4 mg daily on days 1–21 and dexamethasone 20 mg weekly until progression. The primary endpoint was an improved response to treatment. A total of 75/100 patients reached therapy. The median follow‐up time was 73 months. The median duration of treatment was 23.7 months. One third of patients improved their response from the initiation of treatment: 11%, 19% and 4% to a very good partial response, complete response or stringent complete response respectively. The median progression‐free survival time was 33.2 months and the median overall survival time was not reached. Among the 75 patients, the reasons for pomalidomide discontinuation were progressive disease (54%), adverse events (AEs) (30%), investigator discretion (11%) and consent withdrawal (5%). Grade (G) 3/4 haematological AEs included neutropenia (51%) and lymphopenia (35%); G3/4 drug‐related non‐haematological AEs (>5%) comprised 13% infections. Long‐term administration of pomalidomide and dexamethasone is feasible and one third of the patients improved their response.
Summary
High‐dose melphalan followed by autologous haematopoietic stem cell transplantation is widely used in newly diagnosed multiple myeloma (MM) patients as upfront therapy. However, the safety ...and efficacy of transplantation in patients with renal insufficiency (RI) are controversial. We followed a multicentre (16 SFGM‐TC centres) prospective cohort of 50 newly diagnosed MM patients with a serum creatinine clearance of <40 mL/min at transplantation. Patients received a recommended dose of melphalan of 140 mg/m2. The primary end‐point was the non‐relapse mortality at Day 100. One death occurred during the first 100 days post‐transplant. The median time to neutrophil engraftment was 12 days and to platelet engraftment was 13 days. The haematological response improved in 69% of patients, with best responses from partial response (PR) to very good partial response (VGPR) (10%), from PR to complete response (CR)/stringent complete response (sCR) (16%), from VGPR to CR/sCR (39%) and from CR to sCR (2%). At 2 years, the overall survival was 84%, the progression‐free survival was 70% and the cumulative incidence of relapse was 20%. The renal response improved in 59% of patients, with the best renal responses post‐transplant being minimal (9%), partial (2%) and complete (48%). Autologous transplantation was safe and effective in myeloma patients with RI at transplant.
We present the case of a dialyzed patient with relapsed IgA and lambda free light chain multiple myeloma treated with elranatamab. Despite end-stage renal impairment, the treatment with anti-B cell ...maturation antigen (BCMA)xCD3 bispecific antibody proved to be feasible, without unexpected side effects. Increased attention to infectious risk is crucial for these doubly fragile patients.
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