We already know that patient with multiple myeloma have an increased risk of COVID complications and death compared to the general population. Some of these reasons including patients with progressive disease, patients who are over 60 and patients who have kidney problems. Most (limited) results in COVID clinical trials show that myeloma patients can develop COVID antibodies, regardless of which myeloma treatment they are on. However, French myeloma researchers in a recent study showed that patients on anti-CD38 monoclonal antibodies (i.e. daratumumab and isatuximab) have a harder time developing COVID antibodies and these myeloma therapies could impair vaccine responses.

It's important to understand why some patients don't develop antibodies, not only because this knowledge helps protect myeloma patients, but because additional COVID variants can continue to expand through these immunocompromised patients.  

Between January 2021 to June 2021, the researchers looked at 72 myeloma patients vs. 20 control individuals having received two doses of the Pfizer-BioNTech COVId vaccine at a single center, Assistance Publique – Hôpitaux de Paris (AP-HP), for both the original and delta variants of COVID. Eleven of the 72 patients had already had an active COVID infection more than 3 months before vaccination. At the time of vaccination, 48 patients were treated with an anti-CD38 monoclonal antibody and 24 were not. Patients in the anti-CD28 group had received more prior lines of myeloma treatment and more in this group were on active therapy at the time of the study. In 33 patients, the patients were on chemotherapy as well as anti-CD therapy. Twenty patients in the non-anti-CD38 group were on therapy including immunomodulatory drugs, proteasome inhibitors or a combination of the two. According to the researchers:

IgG levels were decreased in the anti-CD38 group. IgA levels were low and similar between the two groups. These results suggest that MM patients who are actively treated, particularly with anti-CD38 immunotherapies, had an impaired production of SARS-CoV-2 specific IgG and IgA.

IgG levels were significantly higher in myeloma patients who had a prior COVID infection before or after vaccination, compared to those without. There were no COVID recurrences in the 11 patients with previously documented SARS-CoV2 infections.

Factors that impaired COVID antibody responses included having a higher number of treatment lines and having progressive disease. Only the anti-CD38 myeloma treatment was associated with antibody failure response when myeloma-specific therapies were evaluated. 

Of COVID-related deaths at the 39 French hospitals, the researchers focused on peak periods before (Period 1: March-July 2020) and after (Period 2: March - July 2021) vaccination programs started. During Period 1, there were 2764 total deaths and 42 myeloma patient deaths. During Period 2 there were 1842 total deaths and 39 myeloma patient deaths. The prescription of anti-CD38 antibodies were stable between Period 1 and 2. The researchers observed that the proportion of death among myeloma patients receiving anti-CD38 treatment was stable (11 during Period 1 and 17 during period 2), where the number of deaths among patients not receiving anti-CD38 therapy decreased (31 during Period 1 and 22 during Period 2). Their results suggest that anti-CD38 therapy could decrease the efficacy of the COVID vaccine in myeloma patients.

Of note, myeloma patients didn't achieve their strongest levels of COVID antibodies until both doses were received, suggesting that at least two doses were needed for full vaccination.

CD38 is expressed by both normal and cancerous cells. According to the researchers:

These highly active monoclonal antibodies also reduce the frequency of normal bone marrow plasma cell in myeloma patients. Anti-CD38 antibodies also induce a partial natural killer (NK)-cells depletion, which could contribute to immunodeficiency in multiple myeloma receiving these immunotherapies. Accordingly, we observed a significant reduction of polyclonal IgG, but not of lymphocyte count, in multiple myeloma patients treated with anti-CD38 compared to patients receiving alternative therapies.

The researchers conclude that their study had limitations and that more investigation is needed. They summarized by stating that additional strategies like booster shots may help myeloma patients obtain better outcomes in the future.