Comment: Addition of ixazomib to pomalidomide and dexamethasone improves survival for multiple myeloma patients

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Published: 14 Jun 2022
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Dr Paul Richardson - Dana Farber Cancer Institute, Boston, USA

Dr Paul Richardson comments on Dr Peter Voorhees's study on the addition of ixazomib to pomalidomide and dexamethasone improving progression-free survival for multiple myeloma patients processing on lenalidomide as part of first-line therapy.

Lenalidomide (LEN) maintenance and continuous LEN-based induction therapy until disease progression have become standard of care for frontline therapy of multiple myeloma (MM).

The addition of IXA to the POM-DEX backbone improved the depth of response and PFS for pts relapsing on LEN as part of 1st line therapy. 

Hematologic toxicity was increased with the addition of IXA, but side effects were manageable. 

The ease of administration of this all-oral combination allowed for safer, uninterrupted treatment during the COVID pandemic. 

The results should be confirmed in phase III trials but lend support for this regimen as part of 2nd line therapy for this patient population.

Watch Dr Mai's interview on the study here

A very nice presentation led by Dr Peter Voorhees which is the Alliance randomised phase II trial which is 80 patients strong, again just as in DETERMINATION where we had almost 20% African-American representation in our randomised phase II study from the Alliance, our African-American representation was closer to 15%. In that study, which is a very real world study, it was designed to look at the key question of oral therapies in the era of COVID really. Whilst that wasn’t the original intent, obviously, the study enrolled and accrued and was carried out intercedent with the pandemic. What we had was basically a design where we looked at the role of pomalidomide and dexamethasone compared to pomalidomide ixazomib and dexamethasone, i.e. both all-oral regimens, used after first relapse in lenalidomide refractory patients. 

We were very pleasantly surprised to see that the pomalidomide dexamethasone arm performed well, around 7.5 months progression free survival, perhaps I’d hoped for better. But what was remarkable was the performance of the triplet regimen of ixazomib pomalidomide and dexamethasone where the actual progression free survival median was over 20 months, it was 20.35 months. That was highly statistically significantly different in favour of the three drugs over the two. 

But this was an all-oral regimen and what was important was in the study we were enriched for high risk – almost 40% of the patients had high risk cytogenetics. So the fact that we were able to demonstrate that kind of clinical benefit from a three-drug all-oral regimen in lenalidomide refractory patients in the era of the pandemic was an important real world study to share. Certainly in the Alliance we were very pleased because it represented a community-focussed study that was really trying to provide patients and, of course, providers with guidance to relatively simple regimens that can be used for frailer patients, arguably, because it was very well tolerated but also, for that matter, for patients who wanted to minimise clinic visits and take advantage of an active regimen perhaps before embarking on more intensive therapies such as an antibody.