Key Clinical Summary:

• Design/Population: The phase 3 JCOG1911 trial evaluated daratumumab maintenance with or without bortezomib in transplant-ineligible newly diagnosed multiple myeloma patients who achieved partial response after DMPB induction. Of 224 patients, 143 were randomized to daratumumab alone (arm A) or daratumumab plus bortezomib (arm B) maintenance.
• Key Outcomes: No PFS benefit was observed with the addition of bortezomib, and the predictive probability of eventual superiority for Arm B was 5.5%, leading to early study termination. Overall survival was similar between arms. Higher rates of grade ≥ 2 adverse events were reported with the combination, including hematologic toxicity, peripheral neuropathy, and gastrointestinal events.
• Clinical Relevance: Adding bortezomib to daratumumab maintenance did not improve PFS and increased toxicity, supporting daratumumab monotherapy as the preferred maintenance strategy in this setting. Ongoing genomic analyses may clarify biological subgroups that could benefit from intensified maintenance.

Tomotaka Suzuki, MD, Nagoya City University Hospital, Nagoya, Japan, presented interim results at the 2025 ASH Annual Meeting & Exposition from the phase 3 JCOG1911 trial, which evaluated adding bortezomib to daratumumab maintenance in transplant-ineligible newly diagnosed multiple myeloma (MM) patients who responded to daratumumab, melphalan, prednisolone, and bortezomib (DMPB) induction therapy. 

The study found no progression-free survival (PFS) benefit with the addition of bortezomib to daratumumab maintenance therapy and was associated with more adverse events. 

Transcript:

My name is Tomotaka Suzuki from Nagoya City University Hospital, representing the JCOG Myeloma Study Group. Today, I will explain the results of the JCOG1911 phase III study presented at ASH.

JCOG1911 was designed to evaluate the impact of adding bortezomib to daratumumab maintenance therapy in transplant-ineligible newly diagnosed myeloma patients who responded to DMPB therapy—daratumumab, melphalan, prednisolone, and bortezomib. In this study, transplant-ineligible patients were first registered and treated with DMPB for up to 18 courses. Those who responded with at least a partial response could procced to secondary registration were randomized to daratumumab maintenance monotherapy, Arm A, or bortezomib plus daratumumab, Arm B. The maintenance therapy was administered for up to for 24 courses, and the primary point of this study was progression-free survival from second registration.

 In total, 224 patients were first registered, and 143 patients underwent second registration and randomization at the interim analysis conducted. This represented 86% of the target sample size for second registration. Again, the primary endpoint of this study was progression-free survival from secondary registration. The other key secondary endpoint were overall survival from first and secondary registration, adverse events completion of maintenance therapy, and so on.

At the first registration, median age of patients was 74 years, and around 20% had performance status of 2 or more, and 23 page percent patients had high risk cytogenetic abnormalities. The second registration, most adjusted factors such as age and cytogenic abnormalities and depths of response were similar between the arm A and arm B, and the primary end point will be explained now.

In the interim analysis, we evaluated that the arm B could demonstrate PFS improvement using 1-sided hypothesis using log-rank test and 1-sided P-value about 0.848 showing that no improvement in Arm B and the hazard ratio was 1.53 favoring arm A. Interim analysis also demonstrated that the predictive probability of arm B favoring arm A at the final analysis was only 5.5%. The data center committee recommended our determination of this study. Overall survival, the secondary end point, were not apparently different between arms and regarding adverse events. Most of adverse events were grade 2 or over, but more adverse events were found in arm B such as hematological authenticities or peripheral neuropathy or gastrointestinal events.

In conclusion, the JCOG1911 study revealed that adding bortezomib to daratumumab maintenance therapy did not improve PFS in transplant-ineligible patients who responded to DMPB therapy. We are now conducting subgroup analysis or ancillary studies using next generation sequencing with the bone marrow samples at diagnosis and at disease progression. These additional studies will reveal why arm B could not demonstrate superiority in PFS.

Thank you for your attention.

Source:

Suzuki T, Machida R, Sano Y, et al. Role of bortezomib maintenance therapy in the anti-CD38 antibody era: Interim analysis results of a randomized phase III study for transplant-ineligible newly diagnosed multiple myeloma (JCOG1911/B-DASH Study). 2025 ASH Annual Meeting & Exposition. Dec 6-9, 2025; Orlando, FL. Abstract: 370