Paul G. Richardson, MD: We can think a little bit about how we use proteasome inhibition in the context of real-world practice. This is a particularly nice study because it is a real practical document from our colleagues, with lead author Robert Rifkin and his team presenting nice data on the feasibility of long-term proteasome inhibition and translation through the transition from bortezomib to ixazomib within the classroom. .
As you can see in this treatment plan or protocol, as compiled by the team, this included 160 newly diagnosed patients. They switched to ixazomib, lenalidomide and dexamethasone after induction-remission treatment with bortezomib-based treatment. The use of ixazomib was classical in IRd [ixazomib, lenalidomide, dexamethasone] schedule with steroid adjustments by age. If you look at response rates and the best overall responses, it is particularly interesting that this real-world therapy continuity and tolerability transition algorithm over time translates into improved high-quality responses. In this study, I am particularly struck by the fact that VGPR [very good partial response] or CR [complete response] peace in this real world is quite nice. It is solid and you will see that it improves over time. The overall response rate is very decent, but the VGPR or better rate is a solid 55% and about half of these patients, 26%, achieve complete remission. It’s quite interesting. Christina, what do you think?
Cristina Gasparetto, MD: This was a very interesting study. It focused on myeloma patients in the community who are not suitable for clinical trials. Their criteria were not so strict. In fact, 44% of patients were over 75 years of age, so they included an elderly population coming with baggage comorbidities and other problems, which means poorer performance. They were aimed at patients who we do not necessarily target in a clinical trial for various reasons. There were a significant number of patients with renal impairment [function]so patients with other malignancies were excluded from clinical trials.
These patients are now suitable for clinical trials, so can we expose them to a long-term proteasome inhibitor? Can this patient last longer? I don’t know, but it won’t be my first choice for newly diagnosed patients, but I’m glad we have these options for some patients. I was fascinated by the endurance and the fact that the patients were able to last the therapy longer. As you mentioned, the depth of response has improved over time and has not affected the quality of life. They were able to maintain therapy for a long time. It was not my first choice at first, but it is a very good choice for a population of myeloma patients with other problems who will now be able to withstand more aggressive treatment. I’m pleasantly surprised.
Paul G. Richardson, MD: I agree, and that’s so interesting to me about this data: the construct that you can easily switch from bortezomib as a parenteral approach to an oral approach that constantly improves response over time. It’s very nice to have potential data that we can share with patients. You can really say, “We have real-world information from a well-executed protocol,” recognizing all the reservations, proving that you can improve the response nicely over time. The tolerance profile is particularly encouraging, but my attention has been drawn to the fact that the tincture of time really matters. That’s 84 patients. Your initial complete response rate after 3 cycles is 4%, but if you are patient and focus on tolerability – this continuity of treatment, realizing that you must devote this time – then you will see that the CR rate has increased to 26% with another 29 % gains VGPR.
Cristina Gasparetto, MD: Yes, it’s not bad.
Paul G. Richardson, MD: I like it strategically, Christina. You have used boron peptides almost. You have used immunomodulatory treatment. But when a relapse occurs, you have several options.
Transcript adjusted for clarity.