CAR T-cell therapy shows promise for patients with myeloma

CHICAGO — All patients with myeloma responded to treatment with BCMA–specific chimeric antigen receptor T-cell therapy, according to results of an ongoing phase 1 trial presented at the ASCO Annual Meeting.

Perspective from Ajai Chari, MD

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated success in targeting B-cell biomarkers in clinical trials for acute lymphoblastic leukemia and lymphoma. However, there has been limited success with CAR T-cell therapies for targeting other biomarkers for other cancers.

Wanhong Zhao

LCAR-B38M (Legend Biotech) is a type of CAR therapy that specifically targets B-cell maturation protein, or BCMA, which researchers in 2004 discovered plays a role in the progression of multiple myeloma.

“LCAR-B38M CAR T technology exerts quick and reproducible therapeutic effects in refractory and relapsed multiple myeloma patients,” Wanhong Zhao, MD, PhD, associate director of hematology at The Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China, said during a press conference.

Zhao and colleagues infused 35 patients with refractory or relapsed multiple myeloma with a median number of 4.7 (range, 0.6-7) x 10⁶/kg LCAR-B38M CAR T cells.

Median follow-up was 208 days (range, 62-321).

The objective response rate was 100%. Thirty-three patients (94%) showed evidence of clinical remission — via complete or good partial response — within 2 months of receiving therapy.

The researchers continue to follow 19 patients for more than 4 months. Of these, 14 reached stringent complete response criteria; one patient reached partial response and four patients reached very good partial remission criteria.

No patients relapsed after stringent complete response. However, one patient experienced disease progression after very good partial remission. Five patients followed for more than 1 year remained in stringent complete response and had no sign of residual disease in bone marrow.

A majority of adverse events appeared mild and manageable. Cytokine release syndrome — a common side effect of CAR T-cell therapy — occurred in 85% of patients, but was transient, Zhao said. Two patients experienced grade 3 cytokine release syndrome, but recovered after therapy with tocilizumab (Actemra, Genentech/Roche).

Researchers did not observe any neurological side effects or serious adverse events.

“LCAR-B38M technology not only demonstrates outstanding efficacy, but also suggests a great safety profile,” Zhao said.

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Researchers will enroll an additional 100 patients in this clinical trial from China. The researchers look to launch a similar trial in the United States next year, Zhao said.

“I’d like to congratulate the researchers, not just for the data and the implication, but the science behind the research. It is quite revolutionary,” Michael S. Sabel, MD, FACS, William W. Coon collegiate professor of surgical oncology and chief of the division of surgical oncology at University of Michigan Health Systems, an ASCO expert, said during the press conference.

Michael S. Sabel

Sabel emphasized how the study combined personalized medicine and immunotherapy, which is important for patients.

“This opens up the door for really using this precision immunotherapy to expand potential of immunotherapy to a wider net of patients,” Sable said. “Obviously, there is more research to be done ... and work in terms of making the therapy more accessible to patients.” – by Melinda Stevens

Reference:

Fan F, et al. Abstract LBA3001. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.

Disclosure: Zhao reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.

Perspective

Ajai Chari, MD

The utility of a treatment boils down to risk, benefit, cost, and quality of life. A 100% response rate, including several complete responses with single intervention speaks for itself, let alone in relapsed disease. Furthermore , the durability of complete responses also was encouraging in patients who have been followed longer periods of time.

In terms of the toxicity, the cytokine release syndrome is expected and, generally low grade. Can we do a better job of predicting who will get cytokine release syndrome and intervene early? Right now, a grade 3 or grade 4 event is when anti-interleukin-6 therapy is initiated but that represents a pretty sick patient because for example their blood pressures have to drop and they do not respond to fluids. In the future, we need to think about intervening early to prevent patients from getting that sick, to eventually move this treatment fully to the outpatient setting. It isn't clear also whether there were any patients who signed consent but for whom a CAR-T product couldn't be produced.

Speaking to cost, the advantage of CAR T-cell therapy is that it is a one-time intervention. And if leading to a durable remission, although it may be expensive, it would be mitigated by the single-time intervention and durability of the response.

This is an outstanding response rate and to date generally durable as well. The risks are as expected or better than other CAR T-cell products. All of this points to a very favorable risk–benefit

Ajai Chari, MD

Icahn School of Medicine at Mount Sinai

Disclosures: Chari reports financial relationships with Amgen, Array Bio Pharma, Bristol-Myers Squibb, Celgene, Novartis, Janssen, Pharmacyclics and Millenium/Takenda.