Multiple myeloma (MM) is an incurable form of hematological cancer affecting plasma cells, reducing the body’s immunity by building abnormal proteins and decreasing natural antibodies.
According to the Global Cancer Observatory (GLOBOCAN) statistics, the incidence of MM in 2020 was 176,404, while the age-standardized rate remained at 1.8 per 100,000 globally, and the ASR mortality rate was 1.1 per 100,000.Cancer.Net statistics “in 2023, an estimated 35,730 adults (19,860 men and 15,870 women) in the United States will be diagnosed with multiple myeloma. Worldwide, an estimated 176,404 people were diagnosed with multiple myeloma in 2020”.
What are the available Multiple Myeloma therapy options?
Since MM is a systemic cancer, surgery is not a treatment option. Radiation, stem cell transplantation, and drug therapies are applicable. Currently, available drug treatments include:
- Chemotherapy: Cyclophosphamide, Etoposide, Doxorubicin, Liposomal doxorubicin, Melphalan, Bendamustine
- Corticosteroids: Dexamethasone, Prednisone
- Immunomodulating agents (IMiDs): Thalidomide (THALOMID), Lenalidomide (REVLIMID), Pomalidomide (POMALYST)
- Proteasome inhibitors (PI): Bortezomib (VELCADE), Carfilzomib (KYPROLIS), Ixazomib (NINLARO)
- Monoclonal antibodies (mAbs)
- Antibodies against CD38: Daratumumab (DARZALEX), Isatuximab (SARCLISA)
- Antibodies against SLAMF7: Elotuzumab (EMPLICITI)
- Nuclear export inhibitor: Selinexor (XPOVIO)
- BCMA
- Antibody-drug conjugates (ADC): Belantamab mafodotin-blmf (BLENREP)
- CAR-T: Ciltacabtagene autoleucel (CARVYKTI), Idecabtagene vicleucel (ABECMA)
- Bispecific T-cell Engager Antibody (BiTE): Teclistamab-cqyv (TECVAYLI)
Latest advancements in Multiple Myeloma Treatment
BMS’s ABECMA and Janssen’s CARVYKTI are two CAR-T cell therapies indicated in late-line MM settings. However, CAR-T cell therapies are associated with severe adverse events such as cytokine release syndrome (CRS), neurotoxicity, and off-tumor activity. Patients who cannot tolerate cell therapy have limited options. The production and availability of this therapy are inadequate, while the cost remains high.
TECVAYLI is currently the latest drug approved by the US FDA for the treatment of resistant forms of MM. It is the first-in-class bispecific T-cell engager antibody. On June 5th, 2023, Janssen announced long-term data for TECVAYLI, which showed more than 60% ORR with 45.5% complete response or better by nearly five months. Data also demonstrated that a single dose of tocilizumab before TECVAYLI treatment reduced the incidence of the CRS adverse event.
Elranatamab, a BCMA-targeted therapy for MM, is expected to get approval within 2023. Pfizer, in its press release issued on 23 February 2023 regarding elranatamab’s FDA and EMA filing acceptance, shared promising results of patients who “received elranatamab as their first BCMA-targeted therapy” after following up with them for a median of 10.4 months.
The key points of the results are summarized below:
- The majority of patients responded well to the treatment achieving an ORR of 61%
- More than half of the patients (55%) achieved at least a partial response.
- 63% showed progression-free survival at 9 months.
- 70% showed overall survival at 9 months.
- The drug showed a manageable safety profile.
Are Multiple Myeloma patients’ needs met?
Despite multiple drug options with targeted mechanisms of action (MoAs), MM treatment still poses a challenge. Below we mention several reasons why MM patients still have unmet needs.
- Available therapies do not cure MM but can only prolong progression-free and overall survival and improve quality of life.
- Complete responses are rarely observed in MM.
- According to a recent survey by GlobalData, there is a treatment gap in patients with high-risk MM.
- Lack of personalized therapies to target specific genetic mutations
- Few treatment options for patients with drug-resistant MM
- Limited treatment options for heavily pre-treated patients beyond the third-line setting
- Decreased patient compliance, particularly among the geriatrics, because of the parenteral route of administration
- High cost of available drugs; a burden on the patients.
Opportunities for pharma companies lying in Multiple Myeloma Treatment. Where should research focus?
Despite the various treatment options (IMiDs, PIs, and mAbs), MM remains a fatal disease with poor quality of life and a high economic burden. Having no cure, patients become resistant to therapies over time.
Consequently, an unmet need exists for MM treatments with diverse MOAs that can produce durable responses, overcome resistance to prior therapies, and be more tolerable, thus requiring continuous therapy improvements.
Janssen’s TECVAYLI has paved the path toward more BCMA-targeting drugs. Within the next years, we expect more of these drugs, a few of which are the following:
- Linvoseltamab by Regeneron (BCMA targeting BiTE; Phase 3)
- Orvacabtagene autoleucel (BCMA targeting CART; Phase 1/2) and Alnuctamab (Phase 1) by BMS
- TNB-383B, AMG 420, AMG 701 (BCMA targeting BiTE; Phase 1), AMG 224 (BCMA targeting ADC; Phase 1) by Amgen
Evolving research identifies more specific targets introducing new drug classes in MM, such as the GPRC5D and the ubiquitin protein ligase modulators.
Talquetamab is a first-in-class GPRC5D bispecific antibody for heavily pre-treated MM. In its press release issued on 25.10.2022, Janssen shares talquetamab clinical trial results and critical regulatory milestones. Specifically,
- 56.7% of patients treated with talquetamab achieved a very good partial response
- In 2022, talquetamab received the Breakthrough Therapy designation from the US FDA and PRIME designation by the European Commission.
- The drug has obtained orphan drug status from both the US FDA and EMA.
- Data were submitted to FDA and EMA in December 2022 and January 2023, respectively.
- Talquetamab has demonstrated a manageable safety profile.
BMS at ASH 2022 presented the following new treatments (BMS-986393 and Mezigdomide) of its portfolio targeting MM disease.
BMS-986393 is an autologous CAR T cell therapy targeting the GPRC5D receptor. BMS reported that in Phase 1 interim analysis, BMS-986393 had elicited deep and durable responses in subjects with relapsed/ refractory MM (RRMM).
Mezigdomide is a novel ubiquitin-protein ligase modulator (Cereblon E3 Ligase Modulating Drug (CELMoD)). BMS announced that Mezigdomide showed an ORR of 39.6%, PFS of 4.6 months, and a manageable safety profile. BMS has disclosed plans to evaluate Mezigdomide in combination with PIs in Phase 3 trials.
In the upcoming years, several treatment options for late-line MM, with a majority of BCMA targeting therapies, are anticipated. Industries are also exploring novel MOAs to ensure better treatment prognosis for patients with MM.
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#myeloma #MultipleMyeloma #MMSM #bloodcancer #MM #RRMM #cancercare #cancertreatment #oncology #hematology #healthcareconsulting #BCMA #BispecificAntibodies #MultipleMyeloma #Tecvayli #Elranatamab #Talquetamab #Linvoseltamab #Abecma #Carvykti
Sources:
Multiple myeloma – Symptoms and causes – Mayo Clinic.
Estimated number of new cases in 2020, World, both sexes, all ages (excl. NMSC)
Drugs Approved for Multiple Myeloma – NCI
Pfizer’s Elranatamab Receives FDA and EMA Filing Acceptance
Multiple Myeloma: unmet needs abound in this oncology indication.
https://ash.confex.com/ash/2022/webprogram/Paper157945.html
Multiple Myeloma: Statistics | Cancer.Net