Real-world analysis of teclistamab in 123 RRMM patients from Germany.

Teclistamab, a B-cell maturation antigen (BCMA) × CD3 directed bispecific antibody, has shown high response rates and durable remissions in the MAJESTEC-1 trial in patients with relapsed and refractory multiple myeloma (RRMM). We retrospectively assessed efficacy and tolerability in 123 patients treated at 18 different German centers to determine whether outcome is comparable in the real-world setting. Most patients had triple-class (93%) or penta-drug (60%) refractory disease, 37% of patients had received BCMA-directed pretreatment including idecabtagene vicleucel (ide-cel) CAR-T cell therapy (21/123, 17.1%). With a follow-up of 5.5 months, we observed an overall response rate (ORR) of 59.3% and a median progression-free survival (PFS) of 8.7 months. In subgroup analyses, we found significantly lower ORR and median PFS in patients with extramedullary disease (37%/2.1 months), and/or an ISS of 3 (37%/1.3 months), and ide-cel pretreated patients (33%/1.8 months). Nonetheless, the duration of response in ide-cel pretreated patients was comparable to that of anti-BCMA naive patients. Infections and grade ≥3 cytopenias were the most frequent adverse events. In summary, we found that teclistamab exhibited a comparable efficacy and safety profile in the real-world setting as in the pivotal trial.

Tolerability of high dose chemotherapy and autologous stem cell transplantation in elderly patients with multiple myeloma: A single-center retrospective analysis.

PURPOSE OF THE STUDY: In the past years, high dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT)has more extensively been performed in elderly patients with multiple myeloma (MM). Several studies found a similar survival benefit compared to younger patients. The objective of our retrospective study is to analyse the tolerability of HDT + ASCT in elderly patients. PATIENTS AND METHODS: We compared 26 ASCT performed in MM patients ≥65 years to 127 ASCT in patients <65 years by evaluating treatment-tolerability, length of hospital stay and number of transfusions. RESULTS: There was no significant difference in the duration of hospitalisation (16 days (range 14-47) in the elderly vs. 17 days (range 14-71) days, P = 0.0903), median time of cytopenia (neutrophils<500/µl: 5 days (range 4-24) vs. 6 days (range 3-28) days, P = 0.1091; platelets<30 000/µl: 6 days (range 3-36) vs. 7 days (range 0-53) days, P = 0.274) or incidence of, or degree of complications between the two age-groups. Immediate and day 100 treatment related mortality (TRM) was comparable in both groups (3.85% vs. 1.58%, P = 0.4304). CONCLUSION: our findings support the concept that HDT + ASCT can be safely administered as first-line option for well-selected patients≥65 years.

Epigenetic dysregulation of secreted Frizzled-related proteins in multiple myeloma.

We analysed the clinical impact of epigenetic dysregulation of the Wnt pathway in malignant plasma cell disorders. In multiple myeloma (MM) cell lines, aberrant promoter hypermethylation of the secreted Frizzled-related protein (SFRP) genes was a common event, and hypermethylation of SFRP1,-2 and -5 was associated with transcriptional silencing. Among 76 primary patient samples, the frequency of aberrant methylation was 35.5% for SFRP1, 52.6% for SFRP2, 1.3% for SFRP4 and 6.9% for SFRP5. Hypermethylation of SFRP1 and -2 genes was detected in monoclonal gammopathy of undetermined significance and all MM stages including plasma cell leukaemia (PCL), while SFRP5 methylation was restricted to advanced MM stages and PCL. Our data indicate that epigenetic silencing of Wnt antagonists is an early event in MM pathogenesis and that SFRP5 hypermethylation may play a role in disease progression.