Quality of life deserves more attention in haematological malignancies – in the design and reporting of trials, in registries and in clinical practice where it needs to be a bigger part of the conversation.

The limbic spoke to two clinician-researchers with an interest in raising the profile of quality of life in research and practice.

Dr Bianca Devitt, a medical oncologist in the Eastern Health Clinical School at Monash University, heads the patient-reported outcomes (PROs) component of the ALLG NHL33 study of acalabrutinib in previously untreated mantle cell lymphoma.

She told the limbic that the difference in QOL reporting between haematology and oncology studies may be related to the magnitude of benefit with therapies.

For example, there were typically small potential benefits for patients in many adjuvant trials in oncology.

“Most people are cured and then you give chemo which might improve their cure rates by 5% or 10%. Whereas in a lot of the haematological malignancies, the benefits are far greater and so therefore you can understand why the impetus for measuring and reporting QOL is less.”

“If you don’t have treatment you die and if you do have treatment you live. You can see that QOL is probably of much less a concern with those statistics as opposed to [a treatment with] marginal benefits.”

“And it’s especially important if you are doing de-escalation trials as obviously you want to see that the treatments are equivalent but if you can also prove that people have a better QOL, then it is another impetus to do that.”

She said quality of life was possibly more important in those haematological malignancies where people weren’t cured and instead lived with a chronic condition.

“I think it just helps us be able to counsel our patients more effectively. It is really reassuring to say to people that most of the QOL data shows that while you are having treatment or three months later your QOL will dip with intensive treatment but things return to normal. Or you can say to people, ‘Look, it does take a year to get better’.”

“It helps you give people an idea of what is normal and how long it is going to take to recover, at any age, and then if you look at specific populations it also helps people weigh up the pros and cons of maybe having adjuvant treatment.”

Dr Devitt said another challenge with quality of life was the quality of the data.

“Often the QOL data set is much poorer than all the other things mandated in a trial – the CT scans, blood tests, etcetera. It definitely drops off because sometimes these things are collected 6-12 months after treatment is finished.”

“Awareness needs to be raised so it is seen as just as important as every other bit of data that you collect.”

She said even when it was collected, QOL data typically went missing during the reporting of trial results.

“I suppose what has happened traditionally is that data has been collected but when they have published their phase 3 trial, they have published all the efficacy and SAE data and then the QOL data has been published in a secondary journal 6 to 8 to 12 months later as an afterthought.”

She said investigators on one side and journal editors on the other had to work at incorporating QOL data into the initial phase 3 report.

“It’s a push from both sides probably so I think initially you have got to try to do it but it’s got to be supported by editors as well.”

Dr Eliza Hawkes, lymphoma lead and medical oncologist at Austin and Eastern Health, told the limbic the haematology community typically chase CRs which was fine in frontline treatment with curative intent.

“But when we can’t cure these people, maybe a more durable partial response is acceptable – where they are not being hammered by chemo just to get a CR.”

“We have a lot of quite frail, older patients and if we are adopting a mentality that we have to achieve CR and we have to achieve cure and that is our golden chalice, well maybe that isn’t the golden chalice for everybody.”

“We’ve been trying to cure relapsed DLBCL for years and we can’t. So maybe we should be doing more of a combination of trying to palliate these patients better and sequencing them on multiple treatment lines like we do in metastatic bowel cancer. We are keeping people alive for longer but we are not trying to give them all the chemo up front and giving them all the toxicity and poor QOL.”

“I personally don’t believe we are doing as well as we could be and we could be learning from other specialities like oncology for these ones that we can’t necessarily cure.”

Dr Hawkes said she was pleased to see quality of life starting to feature more at meetings such as in oral presentations and sessions at ASH 2020.

“I am pleased to see more about QOL, for example in the Keynote-204 study, because we do have a significant number of patients who we can’t cure.”

She said that the quality of life data favouring pembrolizumab over brentuximab in relapsed or refractory Hodgkin lymphoma supported the efficacy data in Keynote-204.

“We just need to notice QOL and we need to take it more seriously. It’s always been secondary in haematological malIgnancies. I think the attention needs to shift.”

Having patients rather than clinicians reporting and grading adverse events would also change the conversations.

“My patients don’t come in and complain about the single episode of febrile neutropenia they had on day 8 and were in hospital for over 24 hours. They complain about their grade 2 diarrhoea, their grade 2 fatigue or their grade 1 rash.”

“Grade 2 diarrhoea is going to the toilet an extra 4-6 times per day. It’s incapacitating and they call it grade 2. And grade 2 neuropathy is the same – it means you cannot do up your buttons and you can’t open jars and that is a big deal.”

She said those symptoms which are typically glossed over and dismissed in discussions of trial results, are the things patients hate the most.

“Especially in our elderly patients, they don’t want to live badly with no disease. They would rather live well with controlled disease,” she said.

Dr Hawkes said a bigger emphasis on quality of life would add more choice and more depth to the discussion with patients.

She added that there was also action underway to incorporate PROs into the binational ANZ Myeloma and Related Disease Registry and then the Lymphoma and Related Disease Registry.