ASCO 2021: BiSpecific Antibodies Expand Immunotherapy Options for Relapsed/Refractory Myeloma Patients
In a prior article, we shared that a new off-the-shelf bispecific antibody targeting BCMA by Janssen (teclistimab) just received Breakthrough Therapy Designation from the FDA. This makes it likely to be the first bispecific antibody available to myeloma patients as a treatment.
Teclistimab Study Results
That designation was made because of data recently released at the ASCO 2021 conference. Amrita Krishnan, MD of City of Hope Comprehensive Cancer Center in Duarte, California presented updated data based on the higher dose at 1500ug/kg given subcutaneously weekly. This higher dose was given to 40 patients. At a median duration of 6.1 months, follow up data showed:
|Overall Response Rate||65%|
|Very Good Partial Response||58%|
|Median time to first response||1 month|
|Duration of response||Not reached yet|
The majority of responders (85%) at a median follow-up of 7.1 months were alive and continuing treatment.
Teclistimab Side Effects and Safety
Safety was tested for the higher dose with the following results. Keep in mind that Grade 3 or 4 side effects are much more severe.
|Cytokine Release Syndrome||70% at any grade and 0% at Grade 3/4|
|Neurotoxicity||1% and resolved without intervention|
|Infections||45% and 23% at Grade 3/4|
|Injection Site Reactions||50% at Grade 1/2|
|Neutropenia||65% at any grade and 40% at Grade 3/4|
|Anemia||50% at any grade and 28% at Grade 3/4|
|Thrombocytopenia||45% at any grade and 20% at Grade 3/4|
Dr. Krishnan concluded that teclistimab has shown encouraging efficacy and safety compared to other approved drugs for patients who have already relapsed after the three main myeloma classes of drugs. An international Phase 2 expansion study at the higher dose is ongoing.
New Treatments, New Issues
As in every aspect of evolving medicine, with new developments come new issues. Now that we have several BCMA directed therapies leading the way in immunotherapy trials and treatments (teclistamab, ide-cel and cilta-cel), a new need will exist for patients who relapse after these BCMA targeted treatments. What can patients try once they relapse?
To this end, trial updates were presented on a new bispecific antibody called elranatamab (which targets BCMA but allows patients previously exposed to BCMA therapy to enroll) and talquetemab (also a bispecific antibody but has a different target called GPRC5D and allows for prior BCMA exposure).
Dr. Nizar Bahlis of the Arnie Charbonneau Cancer Institute, University of Calgary, presented Phase 1 data from the MagnetisMM-1 trial. Elranatamab moved on to a Phase 2 MagnetisMM-3 study, but on April 20 the FDA paused further enrollment due to 3 cases of Peripheral Neuropathy reported "over time" although it has allowed patients who are enrolled and are benefiting from treatment to continue. FDA review of this product is ongoing.
Dr. Bahlis concluded:
- At doses up to 1000 ug/kg when given subcutaneously weekly had a manageable safety profile for relapsed/refractory myeloma patients
- The safety profile supported the weekly dosing
- At doses greater than 215 ug/kg, there was an overall response rate of 70% and a complete response rate of 30%
- At the higher 1000 ug/kg dose, the overall response rate was higher at 83%
- Elrantamab should be continued to be developed
Jesus Berdeja, MD and Director of Myeloma Research at the Sarah Cannon Research Institute, Nashville, TN presented updates on the MonumenTAL-1 study of talquetemab at the higher dose of 405ug/kg subcuteneous weekly. A Phase 2 study is in progress. The main data is captured in the slide below.
It is important to note that GPRC5D is also expressed on skin and nails and so there are "off target" side effects. At the higher dose, 77% of patients had skin related side effects at Grade 1 or 2 including skin exfoliation, pruritis and rash. Nail disorders were seen in 27% of patients including onychomadesis (a separation of the nail plate from the nail matrix due to a temporary halting of nail growth) and nail dystrophy (distortion and discoloration of normal nail-plate structure).
Happily, for myeloma patients, the multitude of Immunotherapy options in the pipeline is cause for celebration. One can only wonder what we'll be able to report on at ASH 2021!