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Day 2 Highlights from the 20th International Myeloma Society Annual Meeting

Day 2 of IMS brought us some recent findings covering a mix of different drug combinations for both newly diagnosed and relapsed/refractory myeloma. Let’s dig into a big day of updates in myeloma treatment.

Pomalidomide, Velcade, Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Revlimid is a key drug in the treatment of newly diagnosed patients with multiple myeloma. Unfortunately, due to the extensive use of Revlimid (lenalidomide)-containing regimens in the frontline setting and Revlimid-maintenance therapy, patients may develop resistance to treatment early in the disease course. Refractoriness is defined as no response to primary therapy (lenalidomide in our case) or progression within 60 days of the last dose.

Pomalyst (Pomalidomide) is approved for the use in patients who have previously received at least 2 drugs to treat multiple myeloma, including a proteasome inhibitor and Revlimid and have demonstrated disease progression on or within 60 days of completion of the last therapy. The combination of Pomalyst-Velcade (bortezomib), and dexamethasone (PVd) is a preferred option in patients who have received one ore more prior therapies, including those who have received Revlimid and Velcade.

In the first abstract, researchers from Turkey reported updates from the phase 3 OPTIMISMM, which has previously shown that PVd significantly prolonged progression-free survival (that is the length of time during and after treatment in which a patient is living with a disease that does not get worse) compared to Vd (11 vs 7 months).  Participants enrolled in OPTIMISMM had a diagnosis of RRMM and had received 1-3 prior lines of therapy, including at least one round of Revlimid.

Their findings showed that patients who received PVd achieved a median overall survival (that is the length of time a patient survives) of 36 months compared with 32 months among patients treated with Vd. The most common side effects with PVd were low white blood cell counts (54%), burning/tingling in the hands and feet, also known as peripheral neuropathy (48%), and low platelet counts (40%). The researchers conclude that PVd is effective in patients for whom Revlimid is no longer a treatment option, including Revlimid-refractory patients after 1 prior line of therapy.

Venetoclax in Patients with the 11;14 chromosomal translocation

Venetoclax is a selective small‐molecule inhibitor of BCL‐2 that is FDA-approved for the treatment of chronic lymphocytic leukemia and has shown to be effective in treating myeloma patients with a translocation of chromosomes 11 and 14 (t[11;14]). An early phase clinical study showed that combination of venetoclax with plus Kyprolis (carfilzomib) and dexamethasone (VenKd) in RRMM showed an overall response rate (ORR) of 92% in patients who had a t(11;14).

In this abstract, Dr Jonathan Kaufman reported initial safety and efficacy data in patients with t(11;14) RRMM treated with one of 2 doses of Ven (400 or 800 mg) combined with Kyprolis and dexamethasone (Ven400Kd or Ven800Kd) compared to Kd alone.  Their findings showed that patients treated with VenKd 400mg or VenKd 800mg achieved an ORR of 89% and 95%, respectively.  Most common side effects observed were diarrhea, nausea, vomiting and fatigue. The incidence of side effects was higher with the higher dose of venetoclax.

This trial is ongoing and additional results will shed light on the clinical potential of venetoclax for the treatment of patients with t(11;14).

Iberdomide, Velcade, and Dexamethasone (IberVd) in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (NDMM)

Iberdomide is a novel, potent oral cereblon E3 ligase modulator (CELMoD™) with a dual function: activate the immune system and directly kill myeloma cells by inducing the destruction of tumor-promoting proteins known as ikaros and aiolos.

In this abstract, researchers from Canada presented results from an early phase clinical trial that evaluated iberdomide in combination with Velcade and dexamethasone (IberVd). This combination has shown promising preliminary efficacy and safety in patients with RRMM in an early phase clinical trial.

Patients in the trial had untreated symptomatic NDMM, no autologous stem cell transplant planned, nor ineligibility due to age or comorbidities. Their findings showed:

The researchers concluded that IberVd showed high efficacy with deep responses in transplant ineligible patients with NDMM. The safety profile was manageable with no new safety signals, and no pts discontinued due to AEs. These findings support further assessment of iberdomide combinations in the frontline setting.

Be sure to hear what myeloma experts Dr. Sagar Lonial and Dr. Keith Stewart, had to say about the day’s presentations here.

Stay tuned for more updates from the final day at IMS 2023!