The last three abstracts presented on myeloma this year focused on Novel Approaches for Relapsed/Refractory Myeloma. In this session, we learned more about the CELMoD iberdomide and two recently approved agents—the antibody-drug conjugate (ADC) Blenrep (belantamab mafadotin) and Xpovio (selinexor)—and how they are being used in different combination regimens.
A new class of drugs called CELMoDs (cereblon E3 ligase modulators) includes agents such as iberdomide and CC-9480. Drugs in this class are related to the immunomodulatory drugs (IMiDs) Revlimid (lenalidomide) and Pomalyst (pomalidomide), but they are more potent. We first learned about the clinical activity of iberdomide combined with dexamethasone (dex) in patients with relapsed or refractory myeloma at last year’s International Myeloma Workshop meeting (posted here).
In today’s session, international investigators reported on the use of iberdomide-dex in combination with Darzalex or Velcade (ABSTRACT 724). Relapsed or refractory myeloma patients received either iberdomide-Darzalex-dex or iberdomide-Velcade-dex. All patients were refractory to their last prior regimen. The results showed that both treatments had a favorable side effect profile and promising clinical activity—even in patients previously exposed IMiDs, proteasome inhibitors, and anti-CD38 antibodies (Darzalex or Sarclisa). This study is ongoing and phase 3 trials are planned.
We heard about the newest antibody–drug conjugate (ADC)—MEDI2228—during Saturday’s session (see Day 1 blog post, ABSTRACT 179). Today we learned more about Blenrep—the first myeloma ADC to be approved for treatment of relapsed or refractory myeloma patients. Blenrep’s approval was based on its activity as a single agent in heavily pretreated patients. Dr. Suzanne Trudel from the Princess Margaret Cancer Centre in Toronto presented the results of a dose-finding study for Blenrep in combination with Pomalyst-dexamethasone (ABSTRACT 725). The results showed promising efficacy for this combination regimen and side effects were consistent with those of Blenrep (including the eye toxicities called keratopathy) and Pomalyst.
Xpovio is the first drug to be approved in a new drug class called selective inhibitors of nuclear export; it was approved last year in combination with dex for patients who have relapsed or refractory multiple myeloma, have received at least four prior antimyeloma treatment regimens, and are refractory to at least two proteasome inhibitors, at least two IMiDs, and an anti-CD38 monoclonal antibody.
Dr. Christine Chen—also from the Princess Margaret Cancer Centre—presented results on the use of Xpovio in combination with Pomalyst-dexamethasone in 60 patients with relapsed or refractory myeloma (ABSTRACT 726). The results showed:
- 60% of patients who had been previously treated with, or were refractory to Revlimid and had not been previously treated with Pomalyst responded to the combination regimen
- All side effects were management with appropriate supportive care measures or dose modifications
These data support the planned phase 3 trial that will compare Xpovio-Pomalyst-dex with Pomalyst-dex in patients who have previously received proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibodies.
It’s hard to believe, but that’s all from ASH 2020—another year in the books! Be sure to tune in to our webinar on Thursday, December 17 (register here) where Dr. Saad Usmani and Dr. Sandy Wong provide their insights on all key myeloma data presented this year. Happy Holidays and Happy New Year!