Professor Chan Cheah

Haematologists with an interest in lymphoma have been riding a roller-coaster of late – from serious concerns about protecting their vulnerable patients during the COVID-19 pandemic to excitement over new treatments on the horizon.

For an update, the limbic spoke to Professor Chan Cheah, lymphoma lead at the Sir Charles Gairdner Hospital, about what’s new in lymphoma.

Professor Chan said the ASH 2021 Annual Meeting in December delivered a number of phase 3 trials which were potentially going to influence practice.

“The big study in frontline is clearly Polarix. It’s a phase 3 trial comparing R-CHOP to polatuzumab-R-CHP in previously untreated patients with DLBCL.”

“The bottom line is the primary endpoint of PFS is positive with a number need to treat of about 16. This study is interesting because phase 3 trials that actually beat R-CHOP in large cell lymphoma are very rare. I think there have only been 2 or 3 in the last 20 years.”

There was no difference in overall survival – although the study was not powered to address this question – but the toxicity was similar for R-CHP plus pola.  I would say that there is going to be a lot of debate about how to interpret this and what it will mean in the Australian context.”

Professor Chan said he believes it will lead to the US approval of polatuzumab in the frontline for DLBCL.

“Whether it translates to a positive PBAC recommendation without overall survival benefit is uncertain due to polatuzumab vedotin price considerations.”

CAR T-cell therapy

Professor Chan also highlighted the suite of phase 3 studies of CAR-T cell therapy in refractory LBCL presented at ASH 2021.

As previously reported in the limbic, both the ZUMA-7 trial of axi-cel and the TRANSFORM trial of liso-cel versus standard of care and transplant returned positive findings while the BELINDA trial of tisagenlecleucel did not.

“Effectively that means that in the US, axi-cel and liso-cel may become adopted for primary refractory patients or early first relapse (<12 months). Kymriah is going to be left as an option for patients who experience disease progression post-autograft – the current indication.”

“Whether CAR T becomes widely used for primary refractory patients or early relapse after R-CHOP in Australia will again be heavily influenced by the pharmacoeconomics,” he said.

“More generally, there is growing data for the CD20xCD3 bispecifics that is looking very encouraging. There is data for glofitamab in various combinations and data from mosunetuzumab in various combinations.”

“These drugs have high response rates, a suggestion of durability of complete responses in relapsed/refractory aggressive lymphoma – especially for glofitamab – and they are generally well tolerated and available off the shelf. These agents are probably headed for FDA approvals in the next 6-12 months.”

He said many sites in Australia have had patients on the bi-specifics studies “so we’ve got a lot of experience using them.”

“They may represent a valid competitor to anti-CD19 CAR T because of their off-the-shelf availability – meaning they will be able to be used with ease for the majority of Australian sites which are non-CAR T infusion centres at present.”

Professor Chan said rituximab was moving to unrestricted benefit this year after an advocacy campaign, .

He said there had been a lot of inequity with patients who clearly benefited from it but were not able to fulfill one of the very specific indications which had evolved over a long period of time.

“A key example was maintenance rituximab in mantle cell lymphoma where there were 2-3 RCTs which showed an OS benefit and yet it wasn’t reimbursed for that indication whereas it was for follicular lymphoma where there was no OS benefit.”

“A group of clinicians led by Professor Stephen Opat pointed out a gap in the previous reimbursement schedule where there was little economic incentive for the pharmaceutical company involved to address it. To their credit, the PBAC was sensible in how they approached it.”

“I’m pretty optimistic about lymphoma at the moment. There is so much happening.”