Serological responses against seasonal influenza viruses in patients with multiple myeloma treated or untreated with daratumumab after two doses of tetravalent vaccine.

OBJECTIVES: Daratumumab-treated myeloma patients may face increased seasonal influenza risk due to weakened postvaccination immune responses, especially with daratumumab treatment. We aimed to assess humoral responses to boosted influenza vaccination in daratumumab-treated or -untreated patients. METHODS: In a single-center study, we evaluated humoral responses (hemagglutination-inhibition assay) one month following a two-injection (4-weeks apart) influenza vaccination (standard dose) in 84 patients with multiple myeloma (40 with daratumumab in the past year). RESULTS: Seroprotection rates (titer ≥1/40) after the second vaccine injection were low across vaccinal subtypes (except for A-H3N2): 71.3% (A-H3N2), 19.7% (A-H1N1pdm09), 9.9% (B-Victoria), 11.3% (B-Yamagata). Only A-H3N2 seroprotection rates significantly increased with the booster in daratumumab-treated patients (30% (12/40) after one injection vs 55% (22/40) after the boost; P = 0.01).After propensity score weighting, daratumumab was not significantly associated with a reduced likelihood of seroprotection against at least one vaccine strain (OR 0.65 [95% CI: 0.22-1.88]). CONCLUSION: While daratumumab treatment did not lead to a significant reduction in seroprotection rates following influenza vaccination, a booster vaccine injection demonstrated potential benefit for specific strains (A-H3N2) in patients undergoing daratumumab treatment. Nevertheless, the overall low response rates in patients with multiple myeloma necessitates the development of alternative vaccination and prophylaxis strategies.

Anti-SARS-CoV-2 antibody response after 2 and 3 doses of BNT162b2 mRNA vaccine in patients with lymphoid malignancies.

OBJECTIVES: COVID-19 patients affected by haematological malignancies have a more severe course of the disease and higher mortality, prompting for effective prophylaxis. The present study aims to evaluate the humoral response after mRNA vaccination as well as the impact of a third vaccine dose in patients with lymphoid malignancies. METHODS: We conducted a single-centre study, evaluating the serological responses of mRNA vaccination amongst a cohort of 200 patients affected by lymphoid malignancies after two or three doses using an industrial SARS-CoV-2 serology assay for anti-receptor binding domain (RBD) Spike IgG detection and quantification. RESULTS: Among patients with plasma cell disorders, 59 of 96 (61%) had seroconversion (anti-RBD >50 AU/mL), and recent anti-CD38 therapies were associated with lower serological anti-RBD IgG concentrations (median IgG concentration 137 (IQR 0-512) AU/mL vs. 543 (IQR 35-3496) AU/mL; p < 0.001). Patients with B-cell malignancies had a lower seroconversion rate (20/84, 24%) mainly due to the broad usage of anti-CD20 monoclonal antibodies; only 2 of 53 (4%) patients treated by anti-CD20 antibodies during the last 12 months experienced a seroconversion. A total of 78 patients (44 with plasma cell disorders, 27 with B-cell malignancies, and 7 with other lymphomas) received a third dose of vaccine. The seroconversion rate and antibody concentrations increased significantly, especially in patients with plasma cell disorders, where an increment of anti-RBD IgG concentrations was observed in 31 of 44 (70%) patients, with an anti-RBD concentration median-fold increase of 10.6 (IQR 2.4-25.5). Its benefit in B-cell malignancies is uncertain, with only 2 of 25 (8%) patients having seroconverted after the vaccine booster, without increased median antibody concentration. DISCUSSION: A third mRNA vaccine dose significantly improved humoral responses among patients with plasma cell disorders, whereas the effect was limited among patients with B-cell malignancies.

Rituximab plus gemcitabine and oxaliplatin (R-GemOx) in refractory/relapsed diffuse large B-cell lymphoma: a real-life study in patients ineligible for autologous stem-cell transplantation.

There is no established standard treatment for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in patients who are not eligible to receive an intensive treatment. The combination of rituximab gemcitabine and oxaliplatin (R-GemOx) is widely used in this population but data are scarce. We retrospectively collected the data of 196 patients with R/R DLBCL treated with R-GemOx in two French centers over a period of 15 years. The median age of the population was 72 years (range, 24-89), 63% of the patients had an international prognostic index of 3 or higher and 57% were refractory to the last treatment. At the end of R-GemOx treatment, 33% of the patients obtained a complete response. The median progression-free survival (PFS) of the population was 5 months and the median overall survival (OS) was 10 months. Several factors were predictors of unfavorable survival: age over 75 years, international prognostic index of 2 or higher, refractory disease and de novo DLBCL. The median PFS and OS of the patients who obtained a complete response were 22 months and 40 months, respectively. The most significant toxicities were grade 3-4 hematological toxicities (31% of patients). Given its efficacy and tolerability, R-GemOx can be used in patients ineligible for intensive treatment and serve as a basis for new regimen combinations.

Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial.

A previous pilot study with rituximab, gemcitabine and oxaliplatin showed promising activity in patients with refractory/relapsed B-cell lymphoma. We, therefore, conducted a phase II study to determine whether these results could be reproduced in a multi-institutional setting. This phase II study included 49 patients with refractory (n=6) or relapsing (n=43) diffuse large B-cell lymphoma. The median age of the patients was 69 years. Prior treatment included rituximab in 31 (63%) and autologous transplantation in 17 (35%) patients. International Prognostic Index at enrollment was >2 in 34 patients (71%). The primary endpoint was overall response rate after four cycles of treatment. Patients were planned to receive eight cycles if they reached at least partial remission after four cycles. After four cycles 21 patients (44%) were in complete remission and 8 (17%) in partial remission, resulting in an overall response rate of 61%. Factors significantly affecting overall response rate were early (<1 year) progression/relapse (18% versus 54%; P=0.001) and prior exposure to rituximab (23% versus 65%; P=0.004). Five-year progression-free and overall survival rates were 12.8% and 13.9%, respectively. Rituximab, gemcitabine and oxaliplatin were well tolerated with grade 3-4 infectious episodes in 22% of the cycles. These results are the first confirmation from a multicenter study that rituximab, gemcitabine and oxaliplatin provide a consistent response rate in patients with refractory/relapsed diffuse large B-cell lymphoma. This therapy can now be considered as a platform for new combinations with targeted treatments. This trial was registered at clinicaltrial.gov under #NCT00169195.

Whole-body diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient mapping for staging patients with diffuse large B-cell lymphoma.

OBJECTIVE: To design a whole-body MR protocol using exclusively diffusion-weighted imaging (DWI) with respiratory gating and to assess its value for lesion detection and staging in patients with diffuse large B-cell lymphoma (DLBCL), with integrated FDG PET/CT as the reference standard. METHODS: Fifteen patients underwent both whole-body DWI (b = 50, 400, 800 s/mm(2)) and PET/CT for pretreatment staging. Lymph node and organ involvement were evaluated by qualitative and quantitative image analysis, including measurement of the mean apparent diffusion coefficient (ADC). RESULTS: A total of 296 lymph node regions in the 15 patients were analysed. Based on International Working Group size criteria alone, DWI findings matched PET/CT findings in 277 regions (94%) (kappa score = 0.85, P < 0.0001), yielding sensitivity and specificity for DWI lymph node involvement detection of 90% and 94%. Combining visual ADC analysis with size measurement increased DWI specificity to 100% with 81% sensitivity. For organ involvement, the two techniques agreed in all 20 recorded organs (100%). All involved organ lesions showed restricted diffusion. Ann Arbor stages agreed in 14 (93%) of the 15 patients. CONCLUSION: Whole-body DWI with ADC analysis can potentially be used for lesion detection and staging in patients with DLBCL.

Respective prognostic values of germinal center phenotype and early (18)fluorodeoxyglucose-positron emission tomography scanning in previously untreated patients with diffuse large B-cell lymphoma.

BACKGROUND AND OBJECTIVES: Diffuse large B-cell lymphomas (DLBCL) have a variable outcome, and powerful methods of prognostication are needed in order to choose the best treatment for each patient. Immunophenotypic classification of the tumor as germinal center (GC) or non-germinal center-like (nGC) and early response evaluation with 18fluorodeoxyglucose positron emission tomography (18FDG-PET) scanning have been correlated with survival in DLBCL but the two methods have never been evaluated simultaneously in the same patient population. Our aim was to investigate their respective prognostic values in the same series of patients. DESIGN AND METHODS: We investigated the expression of CD10, Bcl-6, and MUM1 in 81 patients with DLBCL evaluated early with 18FDG-PET. The tumors were classified as GC or nGC using the algorithm of Hans et al. The results of both methods were correlated with the patients' characteristics and survival. RESULTS: CD10 was positive in 27/76 (36%), Bcl-6 in 43/74 (58%), and MUM1 in 33/73 (45%) interpretable cases. Thirty-eight (51%) were in the GC group, and 36 (49%) in the nGC group. With a median follow-up of 33 months, estimated 3-year event-free survival (EFS) of the whole population was 67%. There was no influence of GC/nGC phenotype on survival. Three-year EFS was 46% in the early PET-positive group versus 80% in the PET-negative group (p=0.0003). INTERPRETATION AND CONCLUSIONS: The prognostic value of GC/nGC phenotype is not confirmed in this heterogeneous series, whereas early PET findings are confirmed to be a powerful predictor of outcome. The impact of treatment decisions based on early PET results should be evaluated.