Induction and Transplant Outcomes Improve With Quadruplet NDMM Regimen

Stephanie L. Elkins, MD

Division Director, School of Medicine

The University of Mississippi Medical Center

Jackson, MS

CASE SUMMARY

A 54-year-old woman presented with laboratory results including the following:

• Hemoglobin: 7.0 g/dL
• Β2-Microglobulin: 6 mg/dL
• Albumin: 3.2 g/dL
• Calcium: 11.3 mg/dL
• Lactate dehydrogenase: 200 U/L
• Creatinine clearance: 45 mL/min
• Bone marrow: 22% monoclonal plasma cells
• Serum kappa free light chains: 240 mg/L
• Serum monoclonal protein: 5 g/dL

She had no cytogenetic (fluorescence in situ hybridization and karyotyping) abnormalities and had an ECOG performance status of 1. PET/CT scans showed multiple bone lesions in her vertebrae without extramedullary disease. Her diagnosis was Revised International Staging System (R-ISS) stage 2/R2-ISS stage 3 IgG-κmyeloma, and she was identified as being eligible for autologous stem cell transplant (ASCT).

DISCUSSION QUESTION

• How do you decide between triplet and quadruplet regimens for patients with transplant-eligible newly diagnosed multiple myeloma (NDMM)? ​

CHANDAR BHIMANI, MD: Based on the PERSEUS [NCT03710603] and GRIFFIN [NCT02874742] trials—PERSEUS was a phase 3 trial, which showed that quadruplets are much better than the triplets with significant improved progression-free survival [PFS] in the transplant-eligible patients—we have phase 2 data with GRIFFIN, and the phase 3 randomized prospective PERSEUS trial.^1,2

STEPHANIE L. ELKINS, MD: Yes, I think that’s strong evidence. Does anyone else have any reason that they might do a triplet instead of a quadruplet?

VENU MADHAV KONALA, MD: In both those studies, they had better [PFS], as well as minimal residual disease [MRD] negativity with quadruplet compared with triplets. I know we are not using MRD regularly in clinical practice, but all trials are incorporating that right now, and that seems to be an important end point as well.

STEPHANIE ELKINS, MD: I can’t disagree with that. My one hesitation is…that I think multiple myeloma has turned into a chronic illness, and if I’m using 4 drugs up front, and then I lose my 4 drugs, I’ve lost an extra drug. That’s what I’ve heard before from people. But the data are clear that the quadruplets are winning the battle there.

DISCUSSION QUESTION

• What do you consider an adequate/successful treatment response in your patients following induction therapy in the real-world setting?

HARISH MADALA, MD: At least a very good partial response [VGPR] would be a decent response, post induction. If they have a complete response, even better, but at least VGPR as minimum.

ELKINS: Does anybody disagree with that? I don't disagree. Do you all send your patients for transplant? Or do you transplant where you are?

MADALA: We send out it to [The Blood & Marrow Transplant Group of Georgia].

ELKINS: Do they have a requirement for how deep the response has to be before they'll transplant?

MADALA: Not necessarily they don't; a VGPR at least. But I think approximately 4 cycles of induction is the average, so whatever best response we can achieve.

ETHAN TOLBERT, MD: I agree with that, [we want] VGPR or better. I send everybody for transplant unless they're older and infirm. The transplanters recently turned someone back around to me and told me they were transplant ineligible because they didn't have enough family support. I don't presume to make those kinds of judgments.… We're going to place him on daratumumab [Darzalex], lenalidomide [Revlimid], and dexamethasone and try to sure up his social situation so he can get a transplant later. They did collect [cells].

ELKINS: I'm a transplanter…and I firmly believe it has a role in the treatment scheme of multiple myeloma at this juncture. We also don't have a set level that you need to be, but I can't remember ever transplanting anybody that wasn't at least at VGPR. I think that's a good level to look at as an adequate or successful level. The deeper the better, so if you can get a little deeper, that's good. But I think you need to be somewhere close to that to proceed.

_References:

_{1. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2024;390(4):301-313. doi:10.1056/NEJMoa2312054}

_{2. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288}