Dr Lulla said he’s not surprised by this result, explaining that the outcomes for patients with CLL after venetoclax and ibrutinib fail are “well known” to be “extremely poor,” with survival less than 12 months.

The second factor identified that is possibly predictive of outcomes was receipt of allogeneic stem cell transplantation after CAR-T therapy. Patients who were able to undergo transplantation had an 86% lower risk of dying (hazard ratio [HR], 0.14; 95% CI, 0.02-0.97; P <.04) compared with patients who were not.

However, because the study was retrospective and sample size small — only 6 patients underwent transplantation — it’s unclear if allogeneic stem cell transplantation was the sole reason for longer survival. “That analysis is biased by the fact that patients who went out to get an allogeneic stem cell transplant were probably in appropriate shape to get a transplant and had an available donor,” said Dr Lulla.

Dr Gerson, who was also not involved in the study, agreed, and added that at the very least, it’s reassuring to see that allogeneic stem cell transplantation might be a durable option in patients for whom CAR-T therapy hasn’t worked.


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The study also provided a glimpse into treatments received after CAR-T therapy and whether certain treatments were associated with longer survival. In particular, receipt of venetoclax after CAR-T therapy was associated with a reduced likelihood of death (HR, 0.17; 95% CI, 0.03-0.80; P =.02).

Similarly, receipt of ibrutinib after CAR-T therapy was associated with a reduced likelihood of death (HR, 0.16; 95% CI, 0.04-0.68; P =.01). In addition, ibrutinib failure before CAR-T therapy did not necessarily guarantee ibrutinib failure after CAR-T therapy, with an approximately 10-month difference in duration of response (2 months vs 12.25 months, respectively; P =.001).

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At this time, the extent to which drug development will be needed in the post–CAR-T setting in CLL is still unclear, given that the investigational anti-CD19 CAR-T therapies in development have shown varying success rates in CLL and the number of patients treated to date remains small. A pilot trial (ClinicalTrials.gov Identifier: NCT01029366) of 14 patients with CLL at the University of Pennsylvania showed that only 8 (57%) had a response to treatment with an anti-CD19 CAR-T therapy, 4 (29%) of which were complete responses.2

The latest data to come out are the updated results from phase 1/2 TRANSCEND CLL 004 trial, which were reported at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition, in Orlando, Florida. The trial showed a high success rate — 82% of patients with CLL had an overall response with the anti-CD19 CAR-T therapy lisocabtagene maraleucel (liso-cel) — but the study population, again, was small, comprised of only 22 patients.3

The results are encouraging, said Dr Gerson. However, given the study population size, he said the therapy is not yet “ready for prime time.”

Disclosure: Various pharmaceutical companies funded the research presented in the poster. For a full list of author disclosures, please refer to the study abstract and poster.

References

  1. Shadman M, Gauthier J, Sirin Khajavian, et al. Clinical outcomes of CLL patients with relapsed or refractory disease after CD19-specific CAR-T therapy. Poster at: the 2020 Transplantation & Cellular Therapy Meetings; February 19-23, 2020; Orlando, FL. Abstract 154.
  2. Porter DL, Hwang WT2, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7(303):303ra139.
  3. Siddiqi T, Soumerai JD, Dorritie KA, et al. Rapid undetectable MRD (uMRD) responses in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treated with lisocabtagene maraleucel (liso-cel), a CD19-directed CAR T cell product: Updated results from Transcend CLL 004, a phase 1/2 study including patients with high-risk disease previously treated with ibrutinib. Oral presentation at: 61st ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 642.