Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse
Abstract
:1. Introduction
2. Overview of Available Therapies in RRMM
2.1. Immunomodulatory Drugs (IMiDs)
2.2. Proteasome Inhibitors
2.3. Monoclonal Antibodies
2.4. Chemotherapy
2.5. Venetoclax
2.6. Selinexor
2.7. CAR-T/BITE Therapy
3. Clinical Scenarios
3.1. Relapse Due to Lenalidomide Resistance/Refractoriness
3.1.1. Immunomodulation with Pomalidomide
3.1.2. Use of Monoclonal Antibody therapy
3.1.3. Switching to a Different Class of Medication
3.2. Relapse Due to Bortezomib Resistance/Refractoriness
3.3. Relapse Due to Daratumumab Resistance/Refractoriness
3.4. Autologous Stem Cell Transplant
3.5. Managing Myeloma Relapse with Renal Impairment
3.6. Managing Myeloma Relapse with Extramedullary Disease
4. Future Directions
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Response | Definition |
---|---|
Complete response (CR) | Negative immunofixation in the serum or urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells on bone marrow aspirate |
Stringent Complete Response (sCR) | Complete response as defined above plus a normal serum free light chain ratio (FLC) and absence of clonal plasma cells on bone marrow aspirate |
Very Good Partial Response (VGPR) | Serum and urine M-protein detectable on immunofixation but not on electrophoresis -or- >90% reduction in serum M-protein plus urine M-protein < 100 mg on 24 h collection |
Partial Response (PR) |
|
Minimal Response (MR) |
|
Stable Disease (SD) | Not meeting criteria for CR, VGPR, PR, MR, or PD. Generally, not recommended for use as an indicator of response |
Progressive Disease (PD) | Increase of 25% from the lowest confirmed response value in one or more of the following criteria:
|
Clinical Relapse | Any one or more of the following criteria:
|
Relapse from CR | Any one or more of the following
|
Trial | % LEN Refractory | ORR (%) | PFS | OS |
---|---|---|---|---|
NIMBUS (MM-003) POM-loDex vs. HiDex | 92 vs. 95 | 30 vs. 9 | 3.9 vs. 1.9 months (HR 0.50, p < 0.001) | 12.7 vs. 8.0 months (HR 0.73, p = 0.0234) |
STRATUS (MM-010) POM-loDex | 95 | 32.1 | 4.6 months | 11.9 months |
OPTIMISMM POM-BOR-dex vs. BOR-dex | 69 vs. 71 | 82.2 vs. 50.0 | 11.2 vs. 7.1 months (HR 0.65, p < 0.0001) | Data not yet mature |
CASTOR DARA-BOR-dex vs. BOR-dex | 17.9 vs. 24 | 80.5 vs. 50.0 | 9.3 vs. 4.4 months (HR 0.36, p = 0.0002) | 28.9 vs. 32.6 months (HR 0.96, NS) |
CANDOR DARA-Kd vs. Kd | 32 vs. 36 | 90 vs. 67 * and 78 vs. 71 ** | 28.1 vs. 11.1 months (HR 0.46, p < 0.001) | Data not yet mature |
IKEMA ISA-Kd vs. Kd | 32 vs. 34 | NT | NR vs. 15.7 months (HR 0.60, p = 0.56) | Data not yet mature |
APOLLO DARA-POM-dex vs. POM-dex | 79 vs. 80 | 69 vs. 46 ¶ | 9.9 vs. 6.6 months (HR 0.66, p = Sig, NT) | Data not yet mature |
ICARIA ISA-POM-dex vs. POM-dex | 93.5 vs. 91.5 | 59.0 vs. 31.4 | 11.4 vs. 5.59 months (HR 0.593, p = NT) | Data not yet mature |
ELOQUENT-3 (Phase 2) ELO-POM-dex vs. POM-dex | 90 vs. 84 | 53 vs. 26 ¶ | 10.2 vs. 4.7 months (HR 0.56, p = NT) ¥ | 28.3 vs. 16.0 months (HR 0.42, p = NT) ¥ |
BOSTON SEL-BOR-dex vs. BOR-dex | 37 vs. 39 ¶¶ | 67.5 vs. 53.2 | HR 0.63, p = NT PFS duration not reported for LEN ref. subgroup | OS duration not reported for LEN ref. subgroup |
BELLINI VEN-BOR-dex vs. BOR-dex | 20 vs. 28 | NT | NR vs. 14.8 months (HR 0.75, p = NT | HR 1.82, p = NT OS duration not reported for LEN ref. subgroup |
Trial | % Previous BOR Exposure | ORR (%) | PFS | OS |
---|---|---|---|---|
ASPIRE * KRd vs. K-dex | 62–67 vs. 64–66 | NT for subgroup analysis | NT for subgroup analysis | 45.9 vs. 33.9 months, HR 0.82, p = NT |
ENDEAVOR * Kd vs. BOR-dex | 54 vs. 54 | NT for subgroup analysis | 15.6 vs. 8.1 months (HR 0.56, p = NT) | 41.8 vs. 32.7 months (HR 0.851, p = NT) |
TOURMALINE MM1 * IRd vs. Rd | 69 vs. 69 | NT for subgroup analysis | 18.4 vs. 13.6 months (HR 0.74, p = NT) | 53.0 vs. 55.8 months (HR 0.994, p = NT) |
EMN011/HOVON114 (Phase 2) K-POM-dex | 100% | 92 | 26 months | 67 months |
APOLLO DARA-POM-dex vs. POM-dex | 47 vs. 49 | 69 vs. 46 ¶ | 8.3 vs. 6.3 months (HR = 0.73, p = NS, NT) | Data not yet mature |
ICARIA ISA-POM-dex vs. POM-dex | 76.6 vs. 75.2 | 60.2 vs. 32.2 | 11.4 vs. 5.59 months (HR 0.578, p = NT) | Data not yet mature |
ELOQUENT-3 (Phase 2) ELO-POM-dex vs. POM-dex | 78 vs. 82 | 53 vs. 26 ¶ | 10.2 vs. 4.7 months (HR 0.56, p = NT) ¥ | 28.3 vs. 16.0 months (HR 0.42, p = NT) ¥ |
Trial | % DARA Refractory | ORR | PFS | OS |
---|---|---|---|---|
DREAMM-2 Belantamab Mafodotin | 100% | 32% | 2.8 months (95% CI: 1.6–3.6 months) | 13.7 months (95% CI: 9.9–NR) |
DREAMM-3 BEL vs. POM-dex | NT | 41% vs. 36% | 11.2 vs. 7 months (HR 1.03) | 21.2 vs. 21.2 months (HR 1.13) |
MajesTEC-1 Teclistamab | 89.7% | 63% | 11.3 months (95% CI: 8.8–17.1 months) | 18.3 months (95% CI: 15.1-NE)* |
Trial | ORR | PFS | OS |
---|---|---|---|
Myeloma X (ASCT vs. Cy maintenance) | sCR or CR: −39.3 vs. 22.4% VGPR or PR: −43.8 vs. 52.9% | 19 vs. 11 months, HR 0.45, p < 0.0001 | 67 vs. 52 months, HR 0.56, p = 0.0169 |
ReLApsE (ASCT + LEN maintenance vs. LEN-dex) | 77.9% vs. 74.6% (p = 0.57) | 20.7 vs. 18.8 months, HR 0.87, p = 0.34 | NR vs. 62.7 months, HR 0.81, p = 0.37 |
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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Bhatt, P.; Kloock, C.; Comenzo, R. Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse. Curr. Oncol. 2023, 30, 2322-2347. https://doi.org/10.3390/curroncol30020179
Bhatt P, Kloock C, Comenzo R. Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse. Current Oncology. 2023; 30(2):2322-2347. https://doi.org/10.3390/curroncol30020179
Chicago/Turabian StyleBhatt, Parva, Colin Kloock, and Raymond Comenzo. 2023. "Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse" Current Oncology 30, no. 2: 2322-2347. https://doi.org/10.3390/curroncol30020179