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| DRUG WATCH |
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| Year : 2022 | Volume
: 54
| Issue : 5 | Page : 373-376 |
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Long-lasting effect of belantamab mafodotin in heavily pretreated multiple myeloma
Manuel David Gil-Sierra1, Maria Del Pilar Briceño-Casado2, Francisco Javier Julia-Luna2, Maria Dolores Martinez-Moya3
1 Department of Pharmacy, Hospital Universitario Puerto Real, Cadiz; Department of Pharmacology, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain
2 Department of Pharmacy, Hospital General Nuestra Señora del Prado, Toledo, Spain
3 Department of Hematology, Hospital General Nuestra Señora del Prado, Toledo, Spain
| Date of Submission | 16-Jul-2021 |
| Date of Decision | 08-Oct-2022 |
| Date of Acceptance | 09-Nov-2022 |
| Date of Web Publication | 13-Dec-2022 |
Correspondence Address:
Manuel David Gil-Sierra
Calle Playa de Bolonia No 10, Cádiz-11406
Spain
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijp.ijp_563_21
Belantamab mafodotin (BLMF) is an interesting therapeutic alternative for multiple myeloma (MM) patients pretreated with immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies. Scientific evidence on BLMF provides immature data about progression-free survival and overall survival by short follow-up of patients with poor prognoses. Cases with long follow-ups could provide additional information about BLMF. This case reports a patient with MM treated with BLMF who had received nine previous lines of therapy with a follow-up of 11 months. No complete response was obtained. However, no disease progression was observed and the patient was still alive at the end of this work. BLMF showed manageable adverse effects. Our patient presented advanced disease, good functional status at the beginning of BLMF treatment, and elevated levels of lactate dehydrogenase during BLMF therapy. The influence of these last two factors was not evaluated in clinical trials. This relationship should be assessed more deeply in future studies.
Keywords: Antibodies, B-cell maturation antigen, belantamab mafodotin, monoclonal, multiple myeloma
How to cite this article:
Gil-Sierra MD, Briceño-Casado MD, Julia-Luna FJ, Martinez-Moya MD. Long-lasting effect of belantamab mafodotin in heavily pretreated multiple myeloma. Indian J Pharmacol 2022;54:373-6 |
How to cite this URL:
Gil-Sierra MD, Briceño-Casado MD, Julia-Luna FJ, Martinez-Moya MD. Long-lasting effect of belantamab mafodotin in heavily pretreated multiple myeloma. Indian J Pharmacol [serial online] 2022 [cited 2023 Jun 6];54:373-6. Available from: https://www.ijp-online.com/text.asp?2022/54/5/373/363394 |
| » Introduction | |  |
Multiple myeloma (MM) is an incurable hematologic malignancy. The recent incorporation of new molecules – such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 antibodies ‒ has increased overall survival (OS) and progression-free survival (PFS) in MM.[1] There are a large number of regimens of these drugs.[2]
Belantamab mafodotin (BLMF) is an anti-B-cell maturation antigen monoclonal antibody that destroys MM cells. DREAMM-2 (NCT03525678) trial evaluated the activity of BLMF in heavily pretreated transplant-ineligible MM patients or after >100 days of stem-cell transplantation.[3] Patients included in this study showed a median PFS of approximately 3–5 months and immature OS data. Considering the few therapeutic alternatives and poor prognosis of MM patients refractory to IMiDs, PIs, and anti-CD38 monoclonal antibodies, BLMF represents a new hope in this clinical context.
Identification of factors to optimize the results of BLMF in clinical practice is essential. For example, post hoc subgroup analysis of the DREAMM-2 study suggested MM patients without extramedullary disease achieved greater benefit from BLMF therapy according to the overall response data.[3] This case reports our clinical experience and management of a patient with MM treated with BLMF who had received nine previous therapeutic lines.
| » Case Report | | |
A 74-year-old male with IgA-kappa quiescent MM presented CD38+ CD138+ CD56+ phenotype in 25% of cells and CD19–CD20 phenotype in 100% of the cell population. The patient reported disabling bone pain refractory to analgesics after 1 year and tumor infiltration lesions were detected radiologically in iliac wings.
Bortezomib, melphalan, and prednisone (VMP) regimens were indicated. After four cycles, it was interrupted due to excessive toxicity: hypophosphatemia, diarrhea, paresthesia, and thrombocytopenia. Treatment was changed to lenalidomide with dexamethasone and the patient received the first cycle. A decrease in monoclonal component (MC) was detected from the start of MM therapy. However, the patient reported increased bone pain and bone marrow biopsy showed a plasmacytoma with >30% plasma cells. Treatment was replaced by an alternating regimen of vincristine/carmustine/melphalan/cyclophosphamide/prednisone and vincristine/carmustine/doxorubicin/dexamethasone. A complete response was achieved and therapy was suspended after four cycles. Relapse was confirmed after 30 months. Lenalidomide–dexamethasone combination was started and partial response (PR) was obtained. Lenalidomide–dexamethasone was permanently discontinued after 16 cycles. Disease progression (DP) with anemia and thrombocytopenia was observed after 10 months without therapy. Pomalidomide–dexamethasone regimen was selected. PR was reached but pomalidomide–dexamethasone combination was withdrawn due to DP after eight cycles.
The patient still had the Eastern Cooperative Oncology Group (ECOG) 0, Stage IIA regarding Durie and Salmon staging system, anemia, and kappa/lambda free light chain ratio (rFLC) >100. Daratumumab monotherapy was used and PR was obtained. DP appeared after nine cycles. Lenalidomide–dexamethasone retreatment was indicated and PR was recorded. DP was confirmed after five cycles. Considering the good functional status of the patient and cardiopathy absence, carfilzomib–dexamethasone scheme was used. DP with rFLC = 14,360 after seven cycles was detected. The patient was treated with five cycles of subcutaneous VMP until DP with rFLC = 25,252.53.
Finally, 2.5 mg/kg of BLMF every 3 weeks was selected. Mild keratopathy in the right eye was diagnosed. PR was achieved in the second cycle. Abdominal ultrasound was requested due to the progressive elevation of serum levels of asymptomatic lactate dehydrogenase (LDH) since the third BLMF cycle. BLMF dose was reduced to 1.92 mg/kg for grade 2 keratopathy in the fourth cycle, but 2.5 mg/kg of BLMF was indicated in the fifth cycle for keratopathy recovery. PR with serum MC reduction of 82% and 100% urinary was registered. Decrease in kappa light chains was 99.5%. No gastrointestinal alterations were observed. Episodes of hypertransaminasemia and albuminuria delayed the 12th and 14th BLMF cycles for 4 weeks. Thirteen cycles of BLMF were administered at the end of this work. Follow-up was 11 months. Thrombocytopenia was detected during all BLMF cycles. The temporal representation of patient evolution can be consulted in [Figure 1] and analytical data are represented in [Figure 2]. | Figure 1: Temporal representation of patient evolution. MMQ = Quiescent multiple myeloma, MM = Multiple myeloma, MC = Monoclonal component (serum), CR = Complete response, PR = Partial response, SD = Stable disease, VMP = Bortezomib, melphalan, and prednisone, Len-Dex = Lenalidomide with dexamethasone, VBMCP = Vincristine, carmustine, melphalan, cyclophosphamide, and prednisone, VBAD = Vincristine, carmustine, doxorubicin, and dexamethasone, Pom-Dex = Pomalidomide and dexamethasone, BLMF = Belantamab mafodotin
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 | Figure 2: Serum analytical data of the case. (a) platelets, (b) lactate dehydrogenase levels, (c) free light chains, (d) monoclonal component
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| » Discussion | | |
This case reported considerable effectiveness results of BLMF in a patient with heavily pretreated MM. The number of previous therapies and follow-ups was much higher than those described in most patients of DREAMM-2 trial,[3] where there were ≤4 previous lines of therapy in approximately 84% of patients and a median follow-up of 6 months. No DP was recorded in our case after 11 months of treatment, whereas the DREAMM-2 study reported a median PFS of <3 months. Similarly, our patient presented PR for a much longer time than suggested in DREAMM-2 trial. This case was repeatedly treated with PIs and IMiDs before and after receiving daratumumab. There is literature supporting a decrease in response or survival with each subsequent therapy in MM patients pretreated with anti-CD38 antibodies.[4] Considering the difficulty in recruiting patients in this clinical context, cases with long follow-ups could provide additional information to selecting candidates for BLMF.
Our patient presented advanced disease but he showed a good ECOG score. It seems reasonable for future studies to evaluate the efficacy of BLMF in different subgroups based on functional status factors. Patients with a good ECOG score could report better responses to BLMF. Similarly, the elevation of LDH serum levels after the start of treatment with BLMF could be a positive response factor. No tests of extramedullary disease were developed in this patient due to the lack of symptoms, as is done in usual clinical practice.
Moreover, our patient required a dose reduction of BLMF due to keratopathy. Ocular toxicity disappeared with ophthalmological health care and the patient was retreated with the initial dose of BLMF in the following cycle. This supports DREAMM-2 results,[3] keratopathy was the most frequent adverse event and it was resolved in most patients. Alterations in transaminase levels and albuminuria led to significant treatment delays, although they were not frequently recorded in DREAMM-2 trial. The impaired state of heavily pretreated MM patients makes it important to maintain close monitoring of hepatic function.
BLMF is a single agent with new action mechanism for highly refractory MM patients. Daratumumab-based combinations in early lines of treatment provide enormous interest for BLMF. This drug should be evaluated in comparison with selinexor-based schemes, melflufen,[5] or chimeric antigen receptor T-cell therapies. Finally, BLMF schemes with new and standard-of-care treatments could lead to a breakthrough in MM.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
Gil-Sierra Manuel David: membership of an advisory board (consultation fees) and lecture for Janssen Pharmaceutica (reimbursement for attending symposia) of another cancer drug. Briceño-Casado Maria del Pilar: no conflicts of interest to declare. Julia-Luna Francisco Javier: no conflicts of interest to declare. Martinez-Moya Maria Dolores: Janssen, BMS, GSK, Novartis fees.
| » References | | |
| 1. | Mateos MV, Cavo M, Blade J, Dimopoulos MA, Suzuki K, Jakubowiak A, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): A randomised, open-label, phase 3 trial. Lancet 2020;395:132-41.  |
| 2. | Gil-Sierra MD, Gimeno-Ballester V, Fenix-Caballero S, Alegre-Del Rey EJ. Network meta-analysis of first-line treatments in transplant-ineligible multiple myeloma patients. Eur J Haematol 2020;105:56-65. |
| 3. | Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): A two-arm, randomised, open-label, phase 2 study. Lancet Oncol 2020;21:207-21. |
| 4. | Gandhi UH, Cornell RF, Lakshman A, Gahvari ZJ, McGehee E, Jagosky MH, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia 2019;33:2266-75. |
| 5. | Chari A, Vogl DT, Gavriatopoulou M, Nooka AK, Yee AJ, Huff CA, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med 2019;381:727-38. |
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