Case 3: A 49-Year-Old with R/R MM Treated with Bispecifics and Develops Adenoviral Infection


An expert panel discusses the case of a 49-year-old with relapsed/refractory multiple myeloma treated with a BCMA bispecific antibody who develops adenoviral infection.


Saad Z. Usmani, MD, MBA, FACP: I’d like to move on to our third case. Dr Scordo, I believe you’re going to be discussing this particular patient.

Michael Scordo, MD: Yes. M.S. is a 49-year-old woman with stage IIIA, IgG kappa, relapsed/refractory multiple myeloma [R/R MM], and she’s on a bispecific antibody. Her MM was diagnosed in 2012. You see the cytogenetic abnormalities on the myeloma there. She is very heavily pretreated with 10 prior lines of therapy, including proteasome inhibitors, IMiDs [immunomodulatory drugs], anti-CD38 monoclonal antibodies, cyclophosphamide, several autologous transplants, as well as BCMA [B-cell maturation antigen]-directed CAR [chimeric antigen receptor] T-cell therapy. Her comorbidities were hypertension, hypothyroidism, and asthma. The patient had BCMA-directed CAR T-cell therapy with fludarabine and cyclophosphamide conditioning on a study. She initially had achieved a partial response, but then developed progressive disease after about 5 months.

She was then enrolled in a clinical trial for a BCMA bispecific antibody. She tolerated the step-up dosing with grade 1 cytokine release syndrome. During cycle 3, she developed nasal congestion, post-nasal drip, intermittent chills, and myalgias, and her respiratory viral panel was positive for adenovirus. Her x-ray was negative for any evidence of pneumonia. When checked in the blood, her adenovirus PCR [polymerase chain reaction test] was positive, consistent with viremia of the adenovirus. She then developed diarrhea multiple times a day with cramps and abdominal pain, and her stool, not surprisingly, was positive for adenovirus.

The patient had a PET [positron emission tomography]/CT that was done to reassess her response, given her history of extramedullary disease, and she had no abnormal uptake or infiltrates in the lung. And notably, she had fairly severe hypogammaglobulinemia, with an immunoglobulin G level of 240 [mg/dL], and you can see the others there. She had persistent sinusitis symptoms, with congestion, ear pressure, headaches, and post-nasal drip. Despite supportive measures, you can see on the right, she had some maxillary sinus thickening there. She saw ID [infectious disease] and ENT [ear, nose, and throat specialists] to help with guidance.

Her respiratory symptoms were initially managed with supportive care but again persisted. She received antibiotics for a possible superimposed bacterial sinusitis, and then a steroid taper given the persistent symptoms, but had minimal improvement. Ultimately, she decided to undergo endoscopic sinus surgery for chronic rhinosinusitis. And after a few weeks of recovery, the symptoms did improve. She also started IVIG [intravenous immunoglobulin] treatment due to hypogammaglobulinemia, and luckily, the adenovirus PCR in the blood with repetition was trending downward.

The adenovirus viremia ultimately cleared with supportive measures, and the respiratory symptoms lasted for a number of weeks but did improve. The diarrhea symptoms luckily improved, and the patient was able to restart the bispecific antibody. She unfortunately progressed after cycle 5 and had to come off the study.

Saad Z. Usmani, MD, MBA, FACP: This is a very interesting case because we don’t have anything specific to treat this adenovirus. We use therapeutics that we have at our disposal, but this kind of infection is very difficult to get rid of. And as you clearly stated, this is a heavily pretreated patient with myeloma who is immunocompromised, both qualitatively and quantitatively. They did not have a very long-lasting response to BCMA CAR T-cell therapy, and their BCMA bispecific treatment was also interrupted with this infectious episode. They also came off the bispecific fairly quickly after initiating treatment. So it was a very difficult case.

I’m going to go back to you, Michael, because we see more of these presentations in our allo [allogeneic stem cell transplant] patient population. What are your thoughts around incidents of adenovirus infections, in general, in that immunocompromised hematologic malignancy patient population? And what are the general treatment options available for those patients?

Michael Scordo, MD: It’s certainly a problem. We see reactivation in the allo transplant population in general of many of these DNA viruses, the double-stranded DNA viruses, like adenovirus, CMV [cytomegalovirus], EBV [Epstein-Barr virus], etc. Obviously, viremia is one thing, but when you see that level rising, you obviously start to get concerned that the patient will develop what we call viral organ disease or some sort of serious issue related to the virus in the blood. In this case, the concern here was that she had, at the very least, adenovirus enteritis or maybe mild colitis. It’s always difficult to know when to treat these patients because, for one, as you mentioned, we don’t have a lot of great therapies, particularly for adenovirus, unfortunately.

The drugs we do have, one is called cidofovir, which does have activity against adenovirus. Unfortunately, one of the limitations of the drug is that it can cause renal injury, and it’s difficult to give, particularly in patients who have protein in their urine at high levels, which of course many of our patients with myeloma patients do have. And it’s tough to dose it, especially with the issue of renal injury. When adenovirus becomes disseminated, it can be very problematic. Aside from what we think about, like sinusitis, upper respiratory symptoms, and pneumonia, it can cause colitis and even cystitis and renal injury.

What we typically do is follow these patients and track the virus in the blood, and then decide whether to treat based on the severity of the symptoms or organ disease. Luckily, in this patient, we were able to stave off any major treatment and allow the patient’s immune system to recover a bit. But you can imagine that if you were thinking about doing an allo transplant in a patient like this, going into transplant with this type of active virus would be problematic, so we would have to think about active treatment.

One other thing I’ll mention about these viruses is that luckily there are some emerging therapeutics, viral-specific T cells, that are used, at least in study thus far, that look very effective for these double-stranded DNA viruses. Some of them can target multiple viruses at the same time, like adenovirus, EBV, CMV, etc. I think as we treat more and more patients with these bispecifics, we’re going to see the incidence of these viral infections go up. They were probably always there, but I think we’re going to be checking for them more, and we’re going to be seeing more of them.

Transcript edited for clarity.

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