Impact of performance status on overall survival in patients with relapsed and/or refractory multiple myeloma: Real-life outcomes of daratumumab treatment.

BACKGROUND: Little is reported on the real-life impact of daratumumab in relapsed and/or refractory multiple myeloma patients (RRMM). We analyzed a cohort of 156 patients who received daratumumab as a single agent concerning ECOG status, eGFR, cytogenetics, lines of prior treatment, and their impact on survival. RESULTS: Eighty-two (53%) patients were triple refractory, 54 (35%) patients were single or double refractory, and 20 (12%) patients were non-refractory. Following daratumumab treatment, the progression-free survival (PFS) in these groups was 7.2%, 11.4%, and 53% (P < .001), and overall survival (OS) was 34%, 73%, and 58% (P < .001) at 36 months, respectively. Poor ECOG, three lines of prior treatment, and triple refractoriness were all associated with inferior PFS and OS in a multivariate analysis including ECOG, high-risk chromosomal aberrations, refractoriness, number of treatment lines, and eGFR. CONCLUSION: Daratumumab remains an attractive treatment option, especially in patients with poor performance and increased frailty. Furthermore, our observations suggest that patients with ECOG 2 and 3 status require additional supportive and/or palliative therapies to compensate for a potentially effective but encompassing late-line therapy. In conclusion, further prospective studies are needed to elucidate the impact of ECOG 2 and 3 status in patients with RRMM.

Rapid Complete Response to Single-Agent Bcl-2 Inhibitor Venetoclax in a Heart-Transplanted Patient with Triple Refractory Immunoglobulin Light-Chain Amyloidosis.

Immunoglobulin light-chain amyloidosis (AL) is a disease with limited treatment options due to the frailty of patients caused by organ damage. Since the clonal plasma cells often contain the cytogenetic aberration t(11;14), the Bcl-2 inhibitor venetoclax is suggested to have a role in the treatment of AL. Here, we report of a heart-transplanted patient, refractory to multiple therapies, reaching a rapid complete response with single-agent venetoclax.

Translocation (11;14) in newly diagnosed multiple myeloma, time to reclassify this standard risk chromosomal aberration?

OBJECTIVES: The most common translocation in multiple myeloma (MM) is t(11;14)(q13;q32), and its importance as prognostic factor has been controversial. The aim was to analyze its prognostic value. METHOD: In this retrospective study of 469 newly diagnosed myeloma patients, outcomes in patients with (11;14) and standard risk (t(11;14)SR) or high risk (t(11;14)HR) cytogenetics were compared to outcomes of patients without t(11;14) and SR (non-t(11;14)SR) or HR (non-t(11;14)HR), respectively. RESULTS: Overall progression-free survival (PFS) was shorter in t(11;14)SR than non-t(11;14)SR (median 28.9 vs 35.3 months); however, the difference was not significant (P = .2). Overall survival (OS) did not differ significantly between the groups. In the subgroup of patients that did not receive high-dose treatment, PFS was shorter for t(11;14)SR compared to non-t(11;14)SR, 10.6 vs 24.6 months (P = .01). Although OS were shorter for t(11,14)SR compared to non-t(11;14)SR (5-year OS 41.7% vs 63.8%), the difference was not significant (P = .1). In HDT patients, no significant difference was observed for OS or PFS between those with or without t(11;14). CONCLUSION: This study shows that t(11;14) is associated with poorer outcome in MM, particularly in non-high-dose-treated SR patients. It should be considered an intermediate or high-risk marker in these patients.

Upfront bortezomib, lenalidomide, and dexamethasone compared to bortezomib, cyclophosphamide, and dexamethasone in multiple myeloma.

OBJECTIVES: At our center, patients with multiple myeloma (MM) were treated upfront with bortezomib, cyclophosphamide, and dexamethasone (VCD) until cyclophosphamide was replaced with lenalidomide in the combination (VRD). These treatments have never been compared head-to-head in large real-life patient material. METHOD: A retrospective analysis of patients treated with VRD and VCD in the first line, both with and without subsequent high-dose treatment (HDT) and autologous stem cell transplantation. A total of 681 patients were included, 117 receiving VRD (71 with, 46 without HDT) and 564 receiving VCD (351 with, 213 without HDT). RESULTS: Overall response rate (≥partial response) was higher with VRD compared to VCD in the entire VRD group (98% vs 88%, P < 0.001) and in the non-HDT group (98% vs 79%, P < 0.001). Progression-free survival (PFS) at 18 months was longer with VRD compared to VCD in the entire VRD group, the non-HDT group and the HDT group (88% vs 63%, 82% vs 32% and 91% vs 73%, respectively). Overall survival at 18 months was better for VRD-treated patients in the entire VRD group (95% vs 89%, P = 0.048). CONCLUSION: Upfront VRD gives better responses and longer PFS compared to VCD in MM patients with or without subsequent HDT.