Autologous transplant vs oral chemotherapy and lenalidomide in newly diagnosed young myeloma patients: a pooled analysis

Abstract

In newly diagnosed myeloma patients, upfront autologous transplant (ASCT) prolongs progression-free survival 1 (PFS1) compared with chemotherapy plus lenalidomide (CC+R). Salvage ASCT at first relapse may still effectively rescue patients who did not receive upfront ASCT. To evaluate the long-term benefit of upfront ASCT vs CC+R and the impact of salvage ASCT in patients who received upfront CC+R, we conducted a pooled analysis of 2 phase III trials (RV-MM-209 and EMN-441). Primary endpoints were PFS1, progression-free survival 2 (PFS2), overall survival (OS). A total of 268 patients were randomized to 2 courses of melphalan 200 mg/m and ASCT (MEL200-ASCT) and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 (median: 42 vs 24 months, HR 0.53; P<0.001), PFS2 (4 years: 71 vs 54%, HR 0.53, P<0.001) and OS (4 years: 84 vs 70%, HR 0.51, P<0.001) compared with CC+R. The advantage was noticed in good and bad prognosis patients. Only 53% of patients relapsing from CC+R received ASCT at first relapse. Upfront ASCT significantly reduced the risk of death (HR 0.51; P=0.007) in comparison with salvage ASCT. In conclusion, these data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.

First linevsdelayed transplantation in myeloma: Certainties and controversies

“…If on one hand it is true that early ASCT improves PFS rates, on the other hand it is associated with a higher toxicity compared to a treatment with novel agents [56] . It has to be also acknowledged that, whilst almost all randomized studies showed longer PFS for early ASCT, the benefit on OS was not uniformly reported [25,[56][57][58] . The lack of advantage observed in some cases in terms of OS is mainly do to the effective salvage therapy nowadays available, and to the possibility for patients to receive ASCT later in their disease history as a salvage treatment.…”

“…A pooled analysis the two trials showed that in newly diagnosed MM patients, HDM followed by ASCT significantly improved PFS and OS in comparison to MPR or CRD. Patients with favourable baseline conditions, such as a good baseline performance status (PS) (Karnofsky PS ≥ 80%), a low ISS (ISS 1), the absence of high-risk cytogenetic abnormalities [del(17p), t(4;14), t(14;16)] and those that had achieved at least a very good partial response Brioli A. ASCT in MM after induction had the most significant benefit in terms of OS [58] . The reported trials seem to favour upfront ASCT, however a possible caveat of these studies is the notoptimal induction treatment, with the rate of complete responses reported after consolidation (with MPR or HDM) that where lower than those reported at the same time point after other chemotherapy-free induction regimens, such as bortezomib-thalidomide-dexamethasone [13,37,56] .…”

Is there still a role for stem cell transplantation in multiple myeloma?

“…In a pooled analysis of the RV‐MM‐209 and EMN‐441 studies, only 53% of the patients who did not undergo ASCT as part of their first‐line treatment were able to undergo ASCT at relapse. Patients who underwent ASCT upfront not only had longer PFS but also benefited from longer 4‐year PFS2 (71% vs 54%; P < .001) and OS (84% vs 70%; P < .001) in comparison with those who underwent delayed ASCT . It must be noted that the patients in the nontransplant arm were treated with a suboptimal induction and consolidation (Rd‐MPR/CRD) approach in comparison with current 3‐drug regimens including a PI and an IMiD.…”

Bortezomib consolidation post‐ASCT as frontline therapy for multiple myeloma deepens disease response and MRD‐negative rate whilst maintaining QOL and response to re‐treatment at relapse

“…The current paradigm for treating fit patients with newly diagnosed multiple myeloma is induction chemotherapy followed by consolidation with autologous stem cell transplantation (ASCT) (Gay et al , ). Consolidation strategies remain controversial, whereas the benefit of lenalidomide maintenance post‐ASCT has been confirmed in several studies (Mikhael, ).…”