Attending the 64th American Society of Hematology (ASH) Annual Meeting, I am continually reminded of how far we have come in the treatment landscape of multiple myeloma (MM) since I became a nurse I 1991. Acronyms of drug regimens that, for the most part, are no longer used (VAD, VBMCP) except for dexamethasone (dex) and auto stem cell transplant (ASCT). But with the “spoils of riches” comes some challenges – what to use when, how to sequence, whose myeloma will respond to what drugs. Clinical trials (CTs) remain the best objective measure of how to answer some of these questions.
Abstracts (both oral and poster) at the ASH meeting highlighted the spectrum of CTs looking at newly diagnosed multiple myeloma (NDMM) to heavily pre-treated relapsed MM (RRMM).
For many years, the standard of care (SOC) for NDMM was Velcade (bortezomib), Revlimid (Lenalidomide) & Dex (VRD), However the Griffin trial, first reported at 2021 ASH, calls into question if the addition of Darzalex (Daratumumab) should become the SOC. From a disease standpoint, he data suggests improved outcomes with the 4-drug combination. From a perso standpoint, patient reported outcomes (PROs) as reported by Rebecca Silbermann, MD MMS from Knight Cancer Institute, Oregon Health & Science University, Portland, OR, also favor the quad regimen.
Relapsed myeloma does not automatically mean refractory. Refractory indicates the myeloma is no longer responsive to a particular or many therapies. For example, if a person has been off all therapy and experiences relapse of myeloma, this does not indicate refractory state. If a person is currently being treated and has progression while receiving treatment, then the myeloma is considered refractory to the current treatment. The question comes to be, when a person has been exposed to a variety of therapies and lines of therapy (LOT), what are the best-next treatment options.
This was the focus of many sessions as new and combinations of existing therapies were reviewed. Dr. Vincent Rajkumar, MD, Mayo Clinic, Rochester, MN, provided the acronym TRAP to help guide the decision process. Additionally, a person’s tolerance and associated side effects to prior therapy are also weighted. Clinical trial participation is preferential if available.
Treatment options for heavily pre-treated myeloma
Monoclonal Antibodies and Bi-specifics – approved and still in clinical trial:
Dr. Suzanne Trudel, Princess Margaret Cancer Center, Toronto, Canada explained how monoclonal antibodies and bi-specific therapies work, and how they are emerging as a major component of the treatment landscape, especially for RRMM.
Monoclonal antibodies – 3 approved options being used in clinical practice and research from NDMM to RRMM, including maintenance. Side effects include first—infusion reaction, if given IV, and increased risk of infection.
Bispecific Antibodies – 1 approved with others in the pipeline.
- Teclistamab, an off the shelf anti-BCMA immunotherapy was recently FDA approved RRMM, and is being investigated for earlier-line treatment and in the maintenance setting. Potential for cytokine release syndrome (CRS) so requires close monitoring during “step-up” dosing.
- Talquetamab – not yet approved GPRC5DxCD3 immunotherapy. This novel target has the potential for skin/nail/hair side effects.
- Cevostamab – not yet approved FcRH5xCD3 immunotherapy is being trialed as a fixed-duration therapy and use of pre-treatment with tocilizumab to prevent CRS, which is a known side effect of treatment.
Risk of infection was notable for the bispecific therapies.
CelMods were a new class of drug, similar to immunomodulatory drugs (IMIDs) like lenalidomide and pomalidomide, were presented by Dr. Sarah Holstein, MD, PhD from University of Nebraska Medical Center.
Iberdomide (Iber) and Mezigdomide (Mezi) are the two furthest along in clinical trials and are being studied in a variety of ways (NDMM, RRMM, combinations, etc).
She also discussed “Bikes” and “Trikes”, a way of harnessing the effects of NK-Cells, another component to the immune cells.
The amount of research dedicated to treatment of myeloma at all stages of the diagnosis (smoldering, NDMM, RRMM) is stunning and hopeful. In addition to treatment, there are researchers looking at testing and detection (iSTOPMM, Mass Spec) and health-reported quality of life and survivorship. For more information captured at the ASH meeting, please see my Twitter feed at @IMFnurseMyeloma, and follow other Support Group Leaders on Twitter at these handles:
@imfsupport @imfmikemyeloma @johnde1Myeloma @jackMAiello @LindaMyeloma @blondie1746 @MidAtlanticMSG @Daw6Jessie @JillZitzewitz @IMFgailMyeloma @mmyelomaliving @DianeHunterMM
Teresa Miceli, RN BSN OCN
SGL@ASH Nurse Liaison
IMF Nurse Leadership Board