Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: Final analysis of clinically relevant subgroups in GRIFFIN Journal Article
| Authors: | Chari, A.; Kaufman, J. L.; Laubach, J.; Sborov, D. W.; Reeves, B.; Rodriguez, C.; Silbermann, R.; Costa, L. J.; Anderson, L. D.; Nathwani, N.; Shah, N.; Bumma, N.; Holstein, S. A.; Costello, C.; Jakubowiak, A.; Wildes, T. M.; Orlowski, R. Z.; Shain, K. H.; Cowan, A. J.; Pei, H.; Cortoos, A.; Patel, S.; Lin, T. S.; Voorhees, P. M.; Usmani, S. Z.; Richardson, P. G. |
| Article Title: | Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: Final analysis of clinically relevant subgroups in GRIFFIN |
| Abstract: | The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease–negativity (10−5) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a trend toward improved progression-free survival versus RVd (hazard ratio [95% confidence interval]) in patients ≥ 65 years (0.29 [0.06–1.48]), with HRCAs (0.38 [0.14–1.01]), and with gain/amp(1q21) (0.42 [0.14–1.27]). In the functional high-risk subgroup (not MRD negative at the end of consolidation), the hazard ratio was 0.82 (0.35–1.89). Among patients ≥ 65 years, grade 3/4 treatment-emergent adverse event (TEAE) rates were higher for D-RVd versus RVd (88.9% vs 77.8%), as were TEAEs leading to discontinuation of ≥ 1 treatment component (37.0% vs 25.9%). One D-RVd patient died due to an unrelated TEAE. These results support the addition of daratumumab to RVd in transplant-eligible patients with high-risk NDMM. (Figure presented.) : Video Abstract-YjyZJrsb3fs1sAVfK2kfK © The Author(s) 2024. |
| Keywords: | adult; controlled study; treatment response; aged; middle aged; survival rate; major clinical study; overall survival; lenalidomide; clinical trial; constipation; fatigue; mortality; neutropenia; cancer combination chemotherapy; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; cancer patient; comparative study; drug megadose; follow up; antineoplastic agent; progression free survival; bortezomib; multiple cycle treatment; multiple myeloma; phase 2 clinical trial; sensory neuropathy; anemia; leukopenia; nausea; randomized controlled trial; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; peripheral neuropathy; dexamethasone; plasmacytoma; high risk patient; age; monoclonal antibody; arthralgia; backache; coughing; dizziness; dyspnea; fever; lymphocytopenia; pneumonia; lung embolism; chromosome aberration; drug fatality; hypokalemia; insomnia; antibodies, monoclonal; minimal residual disease; multicenter study; diagnosis; clinical evaluation; peripheral edema; limb pain; chromosome translocation; headache; genetic risk; drug therapy; trend study; chromosome deletion; muscle spasm; therapy; induction chemotherapy; upper respiratory tract infection; dysgeusia; post hoc analysis; randomized controlled trial (topic); phase 2 clinical trial (topic); comparative effectiveness; clinical outcome; overall response rate; cancer prognosis; maintenance chemotherapy; consolidation chemotherapy; intention to treat analysis; humans; human; male; female; article; monoclonal antibody therapy; daratumumab; newly diagnosed multiple myeloma |
| Journal Title: | Blood Cancer Journal |
| Volume: | 14 |
| ISSN: | 2044-5385 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-07-08 |
| Start Page: | 107 |
| Language: | English |
| DOI: | 10.1038/s41408-024-01088-6 |
| PUBMED: | 38977707 |
| PROVIDER: | scopus |
| PMCID: | PMC11231363 |
| DOI/URL: | |
| Notes: | Source: Scopus |
