Bortezomib-melphalan-prednisone versus lenalidomidedexamethasone in elderly patients with multiple myeloma - the Real MM phase IV trial

Sep 29, 2026

Uploaded by Levi

The Real MM phase IV trial is the first prospective, multicenter, randomized study comparing bortezomib-melphalan-prednisone (VMP) versus lenalidomide-dexamethasone (Rd) in real-life elderly patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. Transplant ineligibility included age ≥65 or comorbidities, with randomization stratified by frailty and cytogenetic risk. The primary endpoint progression-free survival showed similar overall medians, while overall survival at 36 months favored VMP; safety differences included higher thrombocytopenia with Rd and more neuropathy with VMP. Following daratumumab protocol amendment, updated randomization included daratumumab-containing regimens.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

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Letter to the Editor

Trial design and eligibility

Treatment regimens and endpoints

Patient characteristics and follow-up

Efficacy results (PFS, OS, subgroups)

Safety and adverse events

LETTER TO THE EDITOR Bortezomib-melphalan-prednisone versus lenalidomidedexamethasone in elderly patients with multiple myeloma: the Real MM phase IV trial In patients with newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem-cell transplantation (NTE), the standard first-line therapies until the introduction of daratumumab were bortezomib-melphalan-prednisone (VMP) and lenalidomide-dexamethasone (Rd),1 which were approved on the basis of data from the VISTA and FIRST phase III trials.2,3 To our knowledge, the Real MM trial reported here ([clinicaltrials.gov](clinicaltrials.gov) NCT03829371), funded by the Italian Medicines Agency AIFA (Independent Research program), is the first prospective, multicenter, randomized trial comparing VMP versus Rd in a real-life elderly population of NDMM patients. Transplant ineligibility was defined by age ≥65 years or comorbidities. Patients were stratified by frailty (International Myeloma Working Group [IMWG] Frailty Score: fit vs. intermediate-fit vs. frail patients)4 and cytogenetic risk (high risk [presence of t(4;14), t(14;16), or del(17p)] by fluorescence in situ hybridization [FISH] vs. standard risk) and randomized 1:1 to receive VMP (9 cycles) or continuous Rd per approved schedule. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), progression after the next line of therapy (PFS2), time to next treatment (TNT), quality of life (QoL), and safety. This trial was reviewed and approved by the institutional review boards or independent ethics committees at each of the participating centers. All patients provided written informed consent before participating in the trial, which was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Following the introduction of daratumumab in first-line treatment for NTE patients, the protocol was amended, and, as of July 2022, enrolled patients have been randomized to receivedaratumumab-VMP or daratumumab-Rd. Between 10th January 2019 and 26th January 2022, 231 patients were randomized to receive VMP (N=114) versus Rd (N=117) . Baseline characteristics were well balanced (Table 1) . At the data cut-off (29th May 2023), the median follow-up among surviving patients was 28.94 months (Interquartile Range [IQR]: 20.21-37.13), and 56% of VMP patients completed therapy, while 33.3% of Rd patients remained on treatment, with a median duration of treatment of 16 months (IQR: 5.7-32) ( Online Supplementary Figure S1) . The median PFS was 28.8 versus 26.6 months in the VMP versus Rd arms (Hazard Ratio [HR]: 0. 93, 95% Confidence Interval [CI]: 0.63-1.38, P=0.72) (Figure 1A) . However, the HR changed over time (P from the Grambsch and Therneau test =0.076): 0.64 during the first year of treatment (95% CI: 0.37-1.12, P=0.12) and, thereafter, 1.32 (95% CI: 0.74-2.36, P=0.34) . The prespecified subgroup analysis according to cytogenetic risk showed a significant effect modification in terms of PFS between VMP and Rd (interaction P=0.018), with a median PFS of 30.0 (95% CI: 16. 5-not reached [NR]) versus 10.4 months (95% CI: 7.8-NR) in the high-risk group (HR: 0.33, 95% CI: 0.12-0. 92) and of 22.7 (95% CI: 17.7-39.4) versus 33.3 months (95% CI: 26.1-NR) in the standard-risk group (HR: 1.30, 95% CI: 0.80-2.09) . No significant differences in terms of PFS were observed in other subgroups (Figure 1B) . Overall response rate (71% vs. 73%, P=0.90) and the rates of very good partial response or better (≥VGPR) (49% vs. 44%, P=0.56) were similar in the two arms, with a trend toward a higher complete response or better (≥CR) in the VMP arm (13% vs. 5%, P=0.058) . The estimated 36-month OS was 83% with VMP versus 67% with Rd (HR: 0.52, 95% CI: 0.29-0.93, P=0.028) (Figure 2A) . This advantage was also confirmed after censoring fordaratumumab use in second line (HR: 0. 53, 95% CI: 0.28- 0.99, P=0.045) . A survival a

FAQs

What population did the Real MM phase IV trial study?

Elderly patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, defined by age ≥65 or comorbidities.

What were the primary and key secondary endpoints?

The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate, overall survival, PFS2, time to next treatment, quality of life, and safety.

How did VMP compare with Rd in terms of survival outcomes?

Median PFS was similar between arms, but 36-month overall survival was higher with VMP (83% vs 67%). The OS advantage persisted after censoring daratumumab use in the second line and was also seen in both cytogenetic risk subgroups.

What safety differences were reported between VMP and Rd?

Grade 3–4 treatment-emergent adverse events occurred more often with Rd (52% vs 42%). Notably, thrombocytopenia was higher with Rd, while neuropathy was more frequent with VMP; serious adverse events and treatment-emergent deaths were uncommon.

Sep 29, 2026

Uploaded by Levi