Mantle cell lymphoma patients with few options get access to potentially lifesaving therapy.
CAR T-Cell therapy Tecartus (brexucabtagene autoleucel, Gilead) is now publicly funded for patients with mantle cell lymphoma (a rare subtype of non-Hodgkin lymphoma) who have relapsed or are refractory (r/r MCL) to at least two or more lines of therapy.
Patients can access the treatment at the Alfred (Melbourne), Royal Prince Alfred (Sydney), Peter MacCallum Cancer Centre (Melbourne) and Westmead Hospital (Western Sydney), with more centres expected to follow.
“Patients with MCL whose disease returns after standard treatments such as chemotherapy and BTK inhibitors are in urgent need of effective treatments,” said lymphoma specialist Professor Chan Cheah, from Sir Charles Gairdner Hospital in Perth.
“CAR T-cell therapy can provide some of these patients with a high chance of long-term remission, and this announcement is great news for Australian patients with this condition.”
Four CAR T-Cell therapies are approved for use in Australia, including:
- Ciltacabtagene autoleucel (Carvykti, Janssen-Cilag), for relapsed or refractory multiple myeloma.
- Tisagenlecleucel (Kymriah, Novartis Pharmaceuticals Australia) for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and for children and adults up to 25 years of age with B-cell precursor acute lymphoblastic leukaemia (ALL).
- Brexucabtagene autoleucel (Tecartus, Gilead Sciences) for relapsed or refractory mantle cell lymphoma (MCL) and for B-cell acute lymphoblastic leukaemia (B-ALL).
- Axicabtagene ciloleucel (Yescarta, Gilead Sciences) for relapsed or refractory large B-cell lymphoma (LBCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
Three are publicly funded, with Tecartus joining Kymriah and Yescarta on the Highly Specialised Therapies Program, through the National Health Reform Agreement (NHRA). The program funds new, very expensive treatments (costing $200,000 or more per patient) for use at specific public hospitals. Therapies included in the program are approved by MSAC and funded jointly by the Commonwealth and state governments.
Clinical data informing the decision came from the ZUMA-2 trial, a prospective, single arm study involving 74 patients on a standard dose, followed up for a median of 16.5 months. Results showed that 83.4% of the 74 patients on a standard dose had an overall response compared with 40.4% of patients in comparator studies who received salvage therapies; complete response was seen in 59.5% vs 24.7%; median progression-free survival was 16.2 months compared with 9.2 months in two comparator studies; and, in five comparator studies, median overall survival was 10 months, but median overall survival was not reached in the ZUMA-2 trial. No effect was seen in a lower dose group also included in the trial.
In its consideration of Gilead’s application for public funding, MSAC “agreed with the applicant and the commentary that comparative safety was difficult to draw conclusions on, as the salvage therapy trials did not adequately report toxicity. MSAC considered the toxicity profile of CAR-T therapies to be different than those of salvage therapies”.
The FDA is currently investigating five Car T-cell therapies, including Tecartus, after receiving reports of T-cell malignancies associated with “several products in the class”.
The TGA has said it’s watching this space, noting that “the FDA has stated the overall benefits of these products continue to outweigh their potential risks for their approved uses”.
In a statement, Gilead said that after reviewing more than 15,000 patients treated with Tecartus and Yescarta (also publicly funded in Australia) there was “no evidence” that the therapies caused new malignancies.
“We are confident in the overall safety profile of both Tecartus and Yescarta… We have some of the longest follow-up studies of our clinical trials and real-world evidence registries in the industry for Tecartus and Yescarta,” said the statement.
“These data include five-year overall survival data for Yescarta for patients who previously only had an average life expectancy of 6.3 months. Of these, 92% needed no additional cancer treatments, which is suggestive of a potential cure… Patient safety is our first priority and we have fully cooperated with the FDA’s request for an analysis of our data related this inquiry.”