Professor Joy Ho

An international expert panel including Australian haematologist Professor Joy Ho has delivered consensus guidelines and recommendations for the management and response assessment of CAR T-cell therapy for relapsed and refractory multiple myeloma.

The guidelines, from the International Myeloma Working Group (IMWG) Immunotherapy Committee, include recommendations on patient selection, myeloma treatment before CAR T, and the management of toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

Professor Joy Ho, from the Royal Prince Alfred Hospital and University of Sydney, told the limbic the guidelines will become very relevant in the not too distant future when, hopefully, MSAC approves public funding for the Janssen product cilta-cel (Carvykti).

“Despite the previous experience with lymphoma and acute lymphoblastic leukaemia … it’s important to have these guidelines out because myeloma is a different disease. There are additional characteristics that need to be taken into account.”

For example, regarding patient selection, the guidelines recommend patients who are eligible for both CAR T-cell therapy and T-cell engagers should be considered first for CAR T-cell therapy.

Professor Ho said the sequencing issue was currently a moot point in the Australian setting until the bispecifics were approved for treatment, however the information was still relevant in terms of the choice of clinical trials.

The guidelines, published in The Lancet Oncology [link here], also advise that previous exposure to other B-cell maturation antigen (BCMA)-targeted therapy could negatively affect clinical response to CAR T cells.

Professor Ho said the importance of infection prevention and immunoglobulin support was another specific issue in myeloma.

“Therapy can begin before CAR T-cell therapy and continue for at least the first three-six months after CAR T-cell treatment, with the goal of maintaining the IgG level more than 400 mg per dL. Institutional guidelines for replacement intravenous immunoglobulin should be followed in patients with recurrent infections,” the consensus report said.

It also includes a timeline of immune suppression and infection risks after CAR T-cell therapy, a list of high-risk features for opportunistic infection, and both European Society for Blood and Marrow Transplantation (EBMT) and IMWG recommendations on antimicrobial prophylaxis.

Professor Ho said using CAR T in myeloma may also be associated with an increase in delayed neurotoxicity as noted in the CARTITUDE-1 study [link here], although the incidence remains low.

“Follow-up of a larger population across ongoing CARTITUDE studies is needed to understand the incidence and clinical course of the delayed neurotoxicity, but risk factors appear to include high-grade cytokine release syndrome, previous ICANS, high tumour burden, and rapid expansion of CAR T cells,” the guidelines said.

Professor Ho said many additional CAR Ts were on the way including the fast manufacturing products such as PHE885, a BCMA-directed CAR-T cell therapy from Novartis which has been evaluated in 14 countries including Australia. [link here].