CAR T-Cell Products Among Top Advances in Non-Hodgkin Lymphoma

Praveen Ramakrishnan, MD

CAR T-cell therapy has emerged as a new avenue of treatment for heavily pretreated patients with relapsed/refractory lymphoma, said Praveen Ramakrishnan, MD, an assistant professor in the Department of Internal Medicine at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center.

In relapsed/refractory large B-cell lymphoma (LBCL), results from the phase I TRANSCEND NHL 001 trial (NCT02631044), which were presented at the 2019 ASH Annual Meeting, demonstrated an objective response rate (ORR) of 73% (95% CI, 67%-78%) and a complete response (CR) rate of 53% (95% CI, 47%-59%) with the anti-CD19 CAR T-cell therapy lisocabtagene maraleucel (liso-cel; JCAR017).¹ At 1 year, 54.7% of patients remained in response. In December 2019, a biologics license application was submitted to the FDA for the approval of liso-cel for the treatment of adult patients with relapsed/refractory LBCL after ≥2 prior therapies.

In mantle cell lymphoma (MCL), results from the phase II ZUMA-2 trial (NCT02601313) showcased similar efficacy with the anti-CD19 CAR T-cell therapy KTE-X19 in heavily pretreated patients with relapsed/refractory disease. The treatment elicited a CR rate of 67% and an ORR of 93%.²

“The 2019 ASH Annual Meeting was a very exciting meeting for B-cell and T-cell malignancies,” said Ramakrishnan. “These are exciting times to be practicing and taking care of these patients with difficult-to-treat lymphomas.”

In an interview during the 2020 OncLive^® State of the Science Summit™ on Hematologic Malignancies, Ramakrishnan spotlighted some of the exciting data recently presented across the spectrum of non-Hodgkin lymphoma (NHL) treatment.

OncLive^®: Could you discuss some of the updates in B-cell malignancies that were reported at the 2019 ASH Annual Meeting?

Ramakrishnan: This year, we saw several exciting new developments in the field of NHL. I discussed the results of the TRANSCEND NHL 001 study with lisocabtagene maraleucel in LBCL. This was the largest study population to receive CAR T-cell therapy, and the outcomes were very promising. We saw excellent response rates and durable remissions in difficult-to-treat patients. This agent is likely to be FDA approved in LBCL in the second quarter of 2020, joining axicabtagene ciloleucel (axi-cel; Yescarta) and tisagenlecleucel (Kymriah). We’ve wondered about bridging treatments and the role of treatment after CAR T-cell therapy. Additionally, how can we moderate CAR T-cell therapy, such as bicistronic CAR T-cell constructs? However, new innovations are happening every day and CAR T-cell therapy is here to stay.

One of the talks in the plenary session was about bispecific T-cell engagers (BiTEs) in DLBCL. Stephen J. Schuster, MD, of the Perelman School of Medicine, University of Pennsylvania, presented an abstract on mosunetuzumab, which is an anti-CD20 BiTE that was evaluated in heavily refractory large cell lymphoma. The study included patients who were refractory following CAR T-cell therapy. Even so, we saw impressive responses in this difficult-to-treat population. I believe BiTEs are also here to stay. Again, these offer our patients another avenue of treatment after CAR T-cell therapy.

There was also the Intergroup National Clinical Trials Network S1001 study in limited-stage DLBCL. The trial evaluated whether 4 cycles of chemotherapy could abate the need for further treatment or radiation. The results showed excellent outcomes with limited-duration chemotherapy. [Taken them collectively with the results of] the FLYER trial, which were presented at the 2019 ASH Annual Meeting, we’re beginning to question the role of radiation, especially in patients with good-risk, limited-stage DLBCL. Chemotherapy and limited-duration chemotherapy will likely become the standard.

We also saw exciting data in MCL. Could you discuss the results of the ZUMA-2 trial?

Michael Wang, MD, of The University of Texas MD Anderson Cancer Center, presented the analysis of the ZUMA-2 trial, which evaluated the anti-CD19 KTE-X19 product in MCL. The results look very promising, again, in a very difficult-to-treat patient population. Here too, CAR T-cell therapy is offering a new avenue of treatment for patients.

Do you want to emphasize any other important studies?

Patients with T-cell malignancies represent a heterogeneous and very difficult-to-treat group. We saw updated information from the phase III ECHELON-2 study, which looked at the role of transplant after induction chemotherapy with brentuximab vedotin (Adcetris). We are seeing an added advantage to employing autologous stem cell transplant in [these patients]. I also spoke about targeted agents, such as duvelisib (Copiktra), in T-cell lymphomas.

We also saw an abstract from China regarding natural killer T-cell lymphomas. A regimen comprising dexamethasone, cisplatin, gemcitabine, and pegaspargase was compared with the SMILE regimen [dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide]. This regimen looks very promising; it led to better outcomes compared with the SMILE regimen, and it is less toxic. This may be another practice-changing study from the 2019 ASH Annual Meeting.

In follicular lymphoma, we got some updates on targeted agents and monoclonal antibodies, specifically obinutuzumab (Gazyva) in combination with lenalidomide (Revlimid).

References

1. Abramson JS, Palomba ML, Gordon LI, et al. High durable CR rates in relapsed/refractory (r/r) aggressive B-NHL treated with the CD19-directed CAR T cell product JCAR017 (TRANSCEND NHL 001): defined composition allows for dose-finding and definition of pivotal cohort. Blood. 2019;130(suppl 1; abstr 581). doi: 10.1182/blood.V130.Suppl_1.581.581.
2. Wang ML, Munoz J, Goy A, et al. KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in patients (pts) with relapsed/refractory (r/r) mantle cell lymphoma (MCL): results of the phase 2 ZUMA-2 study. Blood. 2019;134(suppl 1; abstr 754). doi: 10.1182/blood-2019-126064.