Part 1: Reviewing Late-Line Options for Relapsed/Refractory Multiple Myeloma

Faith E. Davies, MD (Moderator)

Professor, Department of Medicine at NYU Grossman School of Medicine

Director, Center for Blood Cancers, Perlmutter Cancer Center

Director, Clinical Myeloma Program, Perlmutter Cancer Center

NYU Langone Health

New York, NY

CASE SUMMARY:

In 2017, at the age of 55, an African-American man was diagnosed with multiple myeloma which was hyperdiploid at Revised Multiple Myeloma International Staging System stage II​. He had a history of hypertension controlled with lisinopril​. He received VRd (bortezomib [Velcade], lenalidomide [Revlimid], and dexamethasone) for 4 cycles, followed by autologous stem cell transplant (ASCT) and achieved a very good partial response. ​He was to receive lenalidomide maintenance until progression​.

Three years later, imaging showed stable disease. He had an ECOG performance score of 0. Fluorescence in situ hybridization determined that he had a 17p deletion. He received Dara-Vd (daratumumab [Darzalex], bortezomib, and dexamethasone). One year later, a CT skeletal survey showed new lytic lesions and his performance score was changed to 2. He had a 17p deletion in 50% of cells, hyperdiploid.

FAITH DAVIES, MD: Essentially we’re just under 5 years into the treatment of a man with multiple myeloma who is young, had an ASCT, a good response for 3 years, and now is relapsing following therapy.

[Does] somebody want to tell me why they chose anything in particular?

AMIR STEINBERG, MD: I chose the triplet regimen. I think ideally I would have maybe sent for chimeric antigen receptor [CAR] T-cell therapy, but it’s hard to come by, it can’t happen right away, and you’ve got to find a center that has a slot. So I thought more practically and that’s why I picked a triplet therapy, maybe pomalidomide [Pomalyst], carfilzomib [Kyprolis], and dexamethasone or something like that.¹

Maybe they’d get the referral [for CAR T-cell therapy], but in the meantime, I’d start them on something else.

DAVIES: It’s kind of interesting, isn’t it? I was trying to figure out what combination I would use because, theoretically, if you go by the license indications for CAR T-cell therapy, I’m not quite sure they’d be quite there yet because they’re certainly supposed to be exposed to 3 or 4 lines.² It depends what you call a “line of therapy”. But they’ve definitely been exposed to lenalidomide and they’re resistant, they’ve been exposed to daratumumab and they’re resistant, and they’ve been exposed to bortezomib and they’re resistant.

ILYA BLOKH, MD: I would definitely not do a doublet. I’d definitely go for a triplet. I think the carfilzomib/pomalidomide is pretty enticing with dexamethasone because you’re substituting both the immunomodulatory drug and the proteasome inhibitor and I know there is activity whenever you go to the new class of each of those drugs.^3,4 So there’s a good chance that that patient [could] still respond.

I mean, honestly, with the CAR T-cell therapy, it puts the patient out of our hands and you still want to maintain, as long as you’re giving effective treatment, it’s nice to continue with the relationship you have. But I would definitely refer the patient to a myeloma specialist and work in conjunction with them. But at the same time, I think that carfilzomib/pomalidomide/dexamethasone is a very effective treatment choice.

MARC BRAUNSTEIN, MD: I think these are all reasonable options. I voted for CAR T-cell therapy, but granted the patient is having a symptomatic relapse and you probably need something to bridge him to the CAR T-cell therapy while you wait for the cells to be [infused]. So if he couldn’t go for CAR T-cell therapy right away, then I still have a little hesitation sequencing the belantamab mafodotin [Blenrep] with CAR T cell, so I’d probably give the patient triplet therapy as bridging, and then try to go for CAR T cell.

DAVIES: I think that’s probably where I would come up, and as you say, what you choose for bridging therapy is 1 thing that is important, and when you refer and how early you refer is also important.

DISCUSSION QUESTION:

• Is a second stem cell transplant an option for this patient?

DAVIES: One of the things we didn’t have as an option was about potentially a second transplant. Dr Suarez Londono, can you discuss the second transplant for this patient?

ANDRES SUAREZ LONDONO, MD: I’m a bone marrow transplanter at NYU. The European Society for Blood and Marrow Transplant did a retrospective analysis on patients that had 17p deletion, and they look into doing an ASCT followed by an ASCT, or autologous transplant followed by [allogeneic] transplant. Although there was no overall survival difference, the relapse-free survival and the progression-free survival were beneficial for the patients that had 17p deletion and had an autologous transplant followed by an allogeneic stem cell transplant.⁵

So I think a referral in this patient with 17p to an allogeneic transplant center makes a lot of sense. There are data that suggest a second transplant makes sense. And even an allogeneic transplant in this setting.

DAVIES: Okay. And the patient having had 3 years with their initial chemotherapy, a second ASCT is potentially an option as well, isn’t it?

SUAREZ LONDONO: That’s also a potential option. It [only needs to be] be more than 6 months, [and this patient is] 3 years from the previous ASCT, but it’s still a potential option, just to try to get to a remission. And if there’s access to a clinical trial, this would be an ideal patient, too.

DAVIES: I think it’s quite interesting that the speed of relapse is one of the other things that’s important when we’re thinking about how we’re going to treat patients. If it’s a slow relapse, then yes, we’ve got time to think about these things, and I think it was Dr Braunstein who mentioned bridging therapy to CAR T cells and so on. But if it’s a quick relapse, then it’s one of those situations where we need to get in there and start treatment relatively quickly.

_References:

_{1. Shah JJ, Stadtmauer EA, Abonour R, et al. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015;126(20):2284-2290. doi:10.1182/blood-2015-05-643320}

_{2. Abecma (idecabtagene vicleucel). Prescribing information. Celgene Corporation; 2021. Accessed March 23, 2022. https://bit.ly/3L9VEBi}

_{3. Dimopoulos MA, Goldschmidt H, Niesvizky R, et al. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial [published correction appears in Lancet Oncol. 2017;18(10):e562]. Lancet Oncol. 2017;18(10):1327-1337. doi:10.1016/S1470-2045(17)30578-8}

_{4. Dimopoulos M, Weisel K, Moreau P, et al. Pomalidomide, bortezomib, and dexamethasone for multiple myeloma previously treated with lenalidomide (OPTIMISMM): outcomes by prior treatment at first relapse. Leukemia. 2021;35(6):1722-1731. doi:10.1038/s41375-020-01021-3}

_{5. Gagelmann N, Eikema DJ, de Wreede LC, et al. Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT. Bone Marrow Transplant. 2021;56(1):210-217. doi:10.1038/s41409-020-01007-w}