Response Rate and Response Predictors to the Pfizer/BioNTech Vaccine in Multiple Myeloma Patients

There are currently three Covid-19 vaccines (Pfizer/BioNTech, Moderna, Johnson & Johnson) approved by the US Food and Drug Administration for emergency use against the spread of Covid-19. There has been some recent literature indicating that healthy patients are better protected than myeloma patients. The question arises then as to how effective these vaccines are for us.

An article, titled “Humoral response rate and predictors of response to BNT162b2 mRNA COVID19 vaccine in patients with multiple myeloma”, published in the most recent issue of the British Haematology Journal provides the answer for the Pfizer/BioNTech vaccine (though, unfortunately for some of us, not for either the Moderna or J&J vaccines). At this point you may wonder what on earth a “humoral response” is. “Humor” is a medieval term for body fluid, and a “humoral response” (also called an antibody mediated response)  involves B cells that recognize antigens or pathogens that are circulating in the lymph [fluid in the lymph nodes] or blood.

The article states the importance of understanding the efficacy of the Covid-19 vaccine in myeloma patients:

“Patients diagnosed with multiple myeloma (MM) were found to be at high risk for significant complications [from Covid-19 infection], with mortality approaching 33% . Moreover, recent data suggest that immunocompromised patients often experience a prolonged disease course and may serve as ‘continuous viral reservoirs’, thereby supporting the development of new viral mutations. Prevention of infections, or at least reducing disease severity, is therefore warranted.”

And, also good to know :

“… considering the relatively low response rates reported in multiple myeloma patients that were vaccinated with anti-influenza or pneumococci vaccines approaching 20%–30% only.”

The study was performed in Tel Aviv, Israel and included a cohort of 171 patients (159 active myeloma patients and 12 smoldering myeloma patients) and 64 age compatible healthy volunteers. The active myeloma patient pool characteristics can be summarized as follows:

Patients were vaccinated 21 days apart, consistent with the manufacturer’s vaccination guidelines. The “best time” to vaccinate the myeloma patients was decided to be:

• Patients treated with Darzalex as a single agent or in combination with immunomodulatory agents and/or proteasome inhibitors (PI): have a 14-days gap between their last Darzalex dose and vaccination (adjusting daratumumab schedule with possible delays)
• Patients treated with proteasome inhibitor with or without dexamethasone:  schedule the vaccinations 7–14 days post therapy
• Patients treated with Revlimid maintenance therapy: continue therapy without interruption

Key results can be summarized as follows:

• None of the multiple myeloma patients developed Covid in the +3-month period after the second vaccination dose
• Response was achieved in 78% of the MM patients compared to 98% in the healthy control group. All smoldering myeloma patients had antibody response to the vaccine.
• Antibody response is quantified through an antibody titer (blood test). The measure is expressed in Units per milli-liter (U/mL). The research team reported the following results:

With respect to the large difference to the antibody titer levels between MM patients that responded to the vaccine and the healthy patients, the researchers specifically state:

“There are currently no sufficient data regarding the clinical significance of achieving a high- versus a low-antibody titer following vaccination and the antibody titer cut-off that predicts an efficient and durable immunity is not yet determined. However, achievement of a higher antibody titer may theoretically predict a longer immunity (as reported for some other vaccines)” [emphasis added]

In other words, medical science does not yet know at which antibody level a patient has solid immunity against Covid exposure following vaccination, though it seems reasonable to assume that “the higher, the better."

Response to the vaccine seems to be impacted by several factors:

• Age : elderly patients show lower response rate (Please be aware that response rate is different from response level. The rate is whether one responds or not, and the response level is quantified by the antibody titer test.
• MM patients that are immune-deficient and requiring intravenous Immunoglobulin G infusions, also show a lower response rate.
• Patients with a lower level of response to their myeloma therapy tend to show lower response rates to Covid vaccination.
• “The highly effective anti-MM agents employed in our patients nowadays, providing deeper and more sustainable disease control compared with those obtained earlier, in the pre-novel agent era, might also contribute to the remarkable response rate to COVID19 vaccine.”
• “Heavily pre-treated patients, reflected by four or more novel anti-myeloma drugs or third or subsequent treatment line, have also experienced lower response rates, reflecting the exhaustion of their immune system mainly attributed to their progressive/refractory disease but also to the accumulated effect of multiple anti-myeloma therapies being given.”
• Patients on Revlimid maintenance therapy show a 100% response rate, and that reflects good disease control and, possibly, an additional immunomodulatory effect of this drug.
• None of the novel anti-myeloma drugs administered to the patients seemed to impact responsiveness to this Covid-19 vaccine (to a statistically significant level).

The researchers conclude:

”…, considering the poor outcome of MM patients infected with COVID19, together with the high seropositivity rate to BNT162b2 mRNA COVID19 vaccine, we recommend to vaccinate all MM patients with mRNA anti-COVID vaccine.”

I highly recommend that you read the article referenced above and provided in the link. It is written in very plain, easy to understand English. The full article will not only provide you with some additional knowledge and understanding but will also give you some additional nuances that I was not able to capture in this summary post.