COVID-19 Prevention Gaps in Immunocompromised Patients: Muhammad Bilal Abid, MD

The current landscape of infectious disease treatments is rapidly evolving, but often a subgroup of patients with compromised immune systems is overlooked, said Muhammad Bilal Abid, MD, a clinician scientist at the University of Texas Health Science Center, in an interview with The American Journal of Managed Care^® (AJMC^®).

In the Q&A, Abid discusses key markers in the infectious disease landscape, covering a variety of topics ranging from emerging COVID variants to the National Comprehensive Cancer Network (NCCN) guidelines.

This transcript has been lightly edited for clarity.

AJMC: The CANOPY trial showed no symptomatic COVID-19 cases over 6 months in a small chronic lymphocytic leukemia (CLL) subset receiving pemivibart. How do you interpret these findings in the context of real-world hematology practice, where patients are often on concurrent therapies like BTK inhibitors or venetoclax?

Abid: By definition, CLL is a B-cell-depleting hematologic malignancy. CLL/SLL, the biologic activity of the disease, and then the treatment of the disease—particularly the novel ones, covalent and non-covalent BTK inhibitors—combine to make the patients immunosuppressed beyond just CLL. We really have to be stringent with our infection prevention protocols, using the right type of antimicrobial prophylaxis, and then really thinking about the B-cell depletion component with hypogammaglobulinemia, as B-cell depletion confers an inherent risk for potentially severe and lethal infections due to a compromised immune system. But the lack of ability to mount responses to vaccines, both in terms of higher rates and adequate titer rates, as well as seroconversion rates, hence CLL really represents a disease where one has to think of pursuing novel platforms. There comes the need for pre-exposure monoclonal bodies, which have demonstrated protection against severe, lethal COVID-19 infections.

Now the CANOPY trial (NCT06039449) had a pretty small subset of CLL; certainly, this calls for conducting similar analyses, prospectively in a disease-specific manner. Until we have that data, we have to continue to protect our patients with the available tools that we have at hand.

AJMC: Pemivibart received emergency use authorization for pre-exposure prophylaxis in immunocompromised populations. What are the biggest barriers to implementation in real-world oncology settings logistically or from a payer/coverage perspective?

Abid: The biggest barriers are a lack of education. People are just not aware of the platform that is available. The standard way of protecting patients against infections is vaccinating them, staying on schedule, and then using antimicrobial prophylaxis and standard infection prevention advice.

Now, as the oncology landscape, particularly the cellular therapy landscape, continues to evolve, our patients continue to live longer, but with a compromised immune system. On the same hand, drug development and infectious disease are significantly lagging behind in infection prevention; the vaccination landscape has lagged behind considerably. There are more FDA approvals in the oncology space per week than in the infectious disease space throughout the entire given year.

But in terms of drug approvals or vaccine approvals, I think this is an area where we have to be novel and find combinations of monoclonal antibodies, vaccinations, and antivirals and really find the right infection prevention protocol customized to each one of our immunocompromised patients.

AJMC: Given the rapid evolution of variants and some evidence of reduced neutralization against newer strains, how confident can clinicians be in the durability of monoclonal antibody–based prevention strategies like pemivibart?

Abid: This platform, specifically, this novel mark on the body, has not been investigated in a disease-specific manner. The CANOPY study was an umbrella study that included subcohorts of a variety of patients who fell into the bucket of the immunosuppressed cohort.

We do need to study and examine this disease in a specific manner, in which we can harness the platform for each of the immunocompromised groups with a degree of certainty. However, this is really all we have. We don't have a lot of other platforms available.

We think of any virus, any upper respiratory virus, non-cytomegalovirus, and herpes virus groups. Then we think, how can we protect our patients, particularly among those who do not respond to vaccinations? We realize that their options are very limited.

What we have currently is something that we can utilize to the benefit of our patients. And it certainly confers in the CANOPY study; it did clearly show a significant benefit in terms of infection prevention.

AJMC: Do you see a future where COVID-19 prevention in high-risk hematologic populations mirrors oncology, using combination approaches (eg, vaccines plus monoclonal antibodies or antivirals) rather than relying on a single modality?

Abid: In order to protect our most immunocompromised patients, a novel approach combining antiviral monoclonal pre-exposure prophylaxis, antibody platforms, and vaccinations is needed. And that's something that we can continue to develop as institutional protocols in a multidisciplinary manner, different teams coming together, risk-stratifying patients according to the underlying conditions. And the treatment that they are receiving and creating sort of institutional protocols of who gets put into severe immunocompromised buckets and who gets into the moderately immunocompromised, and then we can bucket the treatment strategy accordingly.

AJMC: How have the NCCN guidelines evolved in response to COVID-19, and where do you see overlap with emerging preventive strategies like pemivibart for patients with leukemia or lymphoma?

Abid: Unfortunately, NCCN guidelines have lagged behind in terms of keeping up with infection prevention protocols. These guidelines are mainly geared towards providing the updated cancer-directed therapy in a disease-specific manner but acknowledge that drug development across the infectious disease and infection prevention space has lagged behind considerably compared to the oncology space.

In the bigger picture, this goes with a viz in terms of NCCN guidelines and oncology guidelines, keeping up with leveraging novel platforms of infection prevention across those who are severely immunocompromised due to newer and more advanced cancer drugs.