CD19-Directed Antibody-Drug Conjugates for DLBCL

Part 2: Real-World Challenges with CAR T-Cell Therapy in DLBCL

During a live virtual event, Beth A. Christian, MD, discussed real-world challenges of providing timely access to CAR-T cell therapy for patients with diffuse large B-cell lymphoma.

CASE SUMMARY

A 75-year-old man was diagnosed with stage IV, CD10+, CD20+ diffuse large B-cell lymphoma (DLBCL) of the germinal center B-cell–like subtype. He went into remission after receiving 6 cycles of rituximab plus cyclophosphamide plus doxorubicin hydrochloride plus vincristine (R-CHOP), but presented 1 year later with relapsed disease. He received second-line rituximab plus gemcitabine plus oxaliplatin (R-GemOx), with partial response, but 5 months later presented with overt disease progression. Third-line treatment with chimeric antigen receptor (CAR) T-cell therapy was discussed as an option, but the patient declined due to the distance to nearest transplant center.

DISCUSSION QUESTIONS

  • What are the real-world challenges with CAR T-cell therapy in the community setting (eg, access, cost, cell collection, length of hospital stay)?
    • What is your access to CAR T-cell therapy? How feasible is it (logistically) for your patients?
    • If you do refer for CAR T-cell therapy, when do you do that?
    • Who is involved in decision making regarding CAR T-cell therapy versus stem cell transplant (SCT)?
    • Based on your experiences and/or those of your colleagues, do you think CAR T-cell therapy is worthwhile for patients?
    • How do you view the data for CAR T-cell therapy compared with data for other options?
  • Are there specific groups/types of patients you would not want to refer for CAR T-cell therapy?

BETH A. CHRISTIAN, MD: It sounds like some of the real-world challenges with CAR T-cell therapy in the community are access to care, understanding which patients may be potential candidates, and the timing of cell collection. Do you find that when you send patients for CAR T-cell therapy that all [treatment] options are considered, including transplant and bridging therapy?

YACOUB FAROUN, MD: The question that we have is if the patient is a candidate for autologous SCT, which [treatment] comes first? Is it the SCT or CAR T cells? I think we have promising data about CAR T-cell therapy that suggests that it might be better than SCT. But again, is that true? We don’t know.

CHRISTIAN: I think at this point that the approval and the National Comprehensive Cancer Network [NCCN] guidelines [suggest CAR T cells as third-line therapy], although emerging data may change this in the near future. My general approach for a patient who is young and fit and has relapsed/refractory disease [is to see how they respond to] second-line therapy, common regimens being R-ICE [rituximab plus ifosfamide plus carboplatin plus etoposide] or R-GDP [rituximab plus gemcitabine plus dexamethasone plus platinum]. If they achieve a complete response, I would move them on to autologous SCT for consolidation.

I think most centers would consider patients who have anything less than a complete response [to second-line treatment], including a partial response or overt progression, to be candidates for CAR T-cell therapy.

The other situation where patients would be candidates [for CAR T-cell therapy] is relapse after autologous SCT. Probably the least well-defined patient population is patients who are deemed ineligible for autologous SCT based on either age or comorbidities, rather than disease- and response-related factors, who may still be able to tolerate CAR T-cell therapy.

The general thinking is that although CAR T-cell therapy comes with significant risk, it is still perhaps less risky than autologous SCT. [CAR T-cell therapy] still has to be a third- or subsequent-line therapy. So, if a patient was unfit for transplant, got second-line R-GemOx, and had a complete response, then he would be observed without treatment. [If the patient had a] partial response, or at the time of progression, as in this case, CAR T-cell therapy could be considered for him.

I think defining a patient who is eligible for CAR T-cell therapy involves judgment [based on an evaluation of patient factors], such as organ function. In this case, the patient’s [low] renal function may have been a barrier to proceeding. But I think there is a population of patients that probably fit into a category that’s a little bit more nebulous.

YAZAN SAMHOURI, MD: Do you follow this approach for patients [with primary refractory disease] who progress while on R-CHOP or within 6 months of treatment. Do you still take them to R-ICE or R-GemOx?

CHRISTIAN: Yes. Until the approvals come through for CAR T-cell therapy as a second-line treatment, my patients still receive second-line chemoimmunotherapy.

NEENOS ALNOOR, MD: Is there an age limit for CAR T-cell therapy?

CHRISTIAN: Some of the early trials of CAR T-cell therapy set age limits of 70 or 75 years, but there is no defined age limit. CAR T-cell therapy has been offered to patients who are in their 80s, [at least at our institution]. Although, these patients are going to be fit with fewer comorbidities.

In general, what’s been your experience with CAR T-cell therapy? Have you had patients undergo it? Have they come back to your practice? What have you seen in terms of responses?

NIRMALA NATHAN, MD: I do send patients out for CAR T-cell therapy. When my patients with large B-cell lymphoma become refractory, I immediately get in touch with the CAR T cell center and ask them what I can do. [For example, I ask them if the] patient is eligible for transplant or for CAR T cells. They guide me through what therapy we should give. Once a patient receives CAR T-cell therapy, we don’t follow them up; they are followed up by the specialty care center.

SAMHOURI: My experience [with CAR T-cell therapy] has been mixed so far. I think that CAR T-cell therapy is the most beneficial and [easiest to use] for patients with multiple myeloma. DLBCL is in the middle, and then I think it’s a little bit more difficult for patients with acute lymphocytic leukemia, [who are usually under the] age of 25. But I have had 3 patients on CAR T so far, [one in each cancer] type, and the patient with multiple myeloma was the easiest to treat, [the oldest], and did the best. In DLBCL, I think we have more treatment choices. The decision [about which of the 3 late-line DLBCL treatments] to use and when to use them is still made by the center’s therapy team.