EBMT 2021 | CAR-T for myeloma: ide-cel pending FDA approval

Ide-cel, or a BCMA, is expected to get approval very soon in United States and probably in Europe also soon after. And this is going to change our field quite significantly because of significant effectiveness of the CAR T-cell therapy. Responses of 80% in patients with median eight lines of treatment is an outstanding response and also getting CRs and MRD-negativity in these patients. And so, there is significant excitement to now be able to treat these late-stage patients effectively.

As it is very effective treatment, various criterias are going to be considered for which patients to be referred and which patients to be considered for CAR T-cells. So, the general criteria may be driven by what the official FDA approval would be. But what we could predict is that patients who have received at least three prior myeloma treatments – that includes proteasome inhibitor, immunomodulator and anti-CD38 monoclonal antibody – are the primary starting point for patient considerations. Patients should have a progressive disease and knowledge limit patients are over 75. One would have to be judged on an individual basis, but I would not put a number there beyond which currently may or may not be considered.

Patients, of course, must be willing to adhere to a reasonably strict clinic visit schedule for maintaining safety, et cetera. However, a lot of the treatment is expected to be outpatient with a small inpatient component in this case.

If we look at other factors, patients with any disease burden maybe eligible for CAR T-cell therapy. And important consideration for patients getting leukapheresis is that preferably we would want to avoid agents, with an effect on lymphocyte count such as bendamustine melphalan, et cetera, so that we collect good T-cells for preparation of the CAR T-cells. And now any patients with prior treatment, history should be considered including patients who have undergone allogeneic transplantation or other gene therapeutic approaches, et cetera.

Importantly, unlike transplant, certain cardio-respiratory functions are not mandated, but well-managed and compensated cardio-respiratory comorbidities may be considered acceptable, unless patients have an active cardiac issues with congestive heart failure, which is not controlled class three or four, severe non-ischemic cardiomyopathy, and or unstable uncontrolled angina, et cetera.

Renal function, I would suggest a creatinine clearance of 30ml per minute or higher would be acceptable. And patients with CNS involvement of myeloma also should be, and could be, considered for CAR T-cell therapy on an individual basis.

Importantly, patients should not have active viral infection, infection immunity is fine. So, HCV, HBV, HIV, et cetera, needs to be considered.

And finally, patients on chronic immunosuppression should be considered with a possibility to hold those drugs and that decision could be made by the centers, which are considering CAR T-cell therapy. Patients with known hypersensitivity to any component of CAR-T product may or may not be eligible, and patients on anticoagulation should have no active bleeding, and one should be able to safely take patients off for a short period of time from anticoagulation when cytopenias do develop.

So, these are general criteria that are to be considered for patients to go and receive CAR T-cell therapy as this exciting new therapeutic modality becomes available in near future.