Over the past few years, we have seen the alphabet soup of triplet and quadruplet therapies for multiple myeloma explode. Today we will be adding another : IberVd.

The Vd part is an acronym that is familiar to just about all of us myeloma patients: Velcade-dexamethasone.

The “Iber” part stands for “iberdomide”, a compound that has been in clinical trials already for several years and with quite a few scientific papers now discussing the outcomes of these trials.

Iberdomide, also known as CC-220, is a compound that Bristol Myers added to its myeloma armamentarium with the acquisition of Celgene (past marketers of Thalomid, Revlimid and Pomalyst and the developers of the anti-BCMA CAR-T product Abecma).

Iberdomide is a member of “the CRBN (Cereblon) E3 ligase modulators (CELMoDs), the next generation of IMiDs (immunomodulators such as e.g., Revlimid) with broader biological activity  [than Revlimid/Pomalyst].”

Bristol-Myers/Celgene started the clinical studies of iberdomide in October 2016 under a very complex but also very complete study design. Apart from evaluating iberdomide as a monotherapy, the company also included study arms for the following combinations with iberdomide :

• Dexamethasone.
• Dexamethasone + Darzalex
• Dexamethasone + Velcade
• Dexamethasone + Kyprolis
• Dexamethasone (for patients with relapsed/refractory myeloma after anti-BCMA treatment)
• Dexamethasone + Velcade (in newly diagnosed myeloma patients)
• Dexamethasone + Darzalex (in newly diagnosed myeloma patients)

This post, however, will be limited to the discussion of the group of newly diagnosed patients given the combination of IberVd, as presented at the recent International Society Myeloma meeting in Athens, Greece¹.

• Overall response rate (ORR): 100 %
• Complete response rate or better (CR or sCR): 56.25 %
• Very good partial response (VGPR) or better: 87.50 % (with 43 % of patients clocking at MRD- at less than one cell per 100,000)
• 69 % of patients responded within six weeks from the start of treatment
• The median time to first response was three weeks
• Of special note is that the pairing of iberdomide with Velcade and dexamethasone resulted in a 177 % median increase in T-cell proliferation

The dosing schedule is very similar to what many of us have seen in a Velcade-Revlimid-dexamethasone (VRd) induction program following our diagnosis with myeloma :

• First eight (8) cycles of 21 days (“two weeks on, one week off”)
  • Oral iberdomide daily for 14 days
  • Oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11, 12
  • Velcade subcutaneous on days 1, 4, 8, 11
• From the 9^th cycle onwards – cycles if 28 days (“3 weeks on, 1 week off”)
  • Oral iberdomide daily for 21 days
  • Oral dexamethasone 40 mg – once weekly
  • No Velcade

The noted side effects were very similar to those seen with the VRd combo.

• 24 % of patients required a dose reduction in order to mitigate the severity of peripheral neuropathy (not unusual for those of us who have had or are still getting the VRd combo).
• 76 % of patients reported infections with most of those being Covid, followed by pneumonia.
• The incidence of COVID-19 was most likely the direct result of this part of the clinical program straddling the COVID-19 pandemic period.

In summary, “These data support further assessment of iberdomide combinations in the frontline setting”.

Iberdomide has all the makings of becoming an exciting addition to the treatment options for myeloma patients.

Unfortunately, we will have to wait a few more years for this compound to complete its clinical program and for Bristol to compile a regulatory dossier and submit it for review with the FDA, before this drug can be commercialized.

1. White D, Lipe B, Mesa MG, et al. Iberdomide, bortezomib, and dexamethasone (IberVd) in transplant-ineligible newly diagnosed multiple myeloma: results from the CC-220-MM-001 trial. Presented at: 2023 International Myeloma Society Annual Meeting; September 27-30, 2023; Athens, Greece. Abstract OA-41

Other articles on iberdomide: 

• Clinical Trial: Iberdomide Alone or With Dexamethasone in Smoldering Myeloma

• IMW: Iberdomide Demonstrates Ability to Overcome Resistance to Common Myeloma Therapies