Multiple Myeloma Trials and Quality News Reporting With Manni Mohyuddin, MBBS

At the recent 64th American Society of Hematology (ASH) Annual Meeting in New Orleans, Dr. Manni Mohyuddin, Assistant Professor at the University of Utah Huntsman Cancer Institute, sat down with Oncology Data Advisor to discuss the multiple myeloma research he was involved with at this year’s meeting. Dr. Mohyuddin elaborates on his abstracts regarding the prognostic value of (11;14) translocation in multiple myeloma, the characterization of survival end points in clinical trials, and ways to improve the quality of news reporting of oncology clinical trials.  

This podcast episode was recorded live by Oncology Data Advisor and ConveyMED at the 2022 ASH Annual Meeting in New Orleans.

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we’re at the ASH Annual Meeting, and I’m here with Manni Mohyuddin. Thank you so much for joining today.

Manni Mohyuddin, MBBS: The pleasure is mine, thank you.

Oncology Data Advisor: So, I know you have a few abstracts here at the meeting. Would you like to tell us about these and give a little overview of them?

Dr. Mohyuddin: Absolutely. One of the abstracts that we have here looks at the prognostic value of (11;14) translocation in patients with multiple myeloma receiving anti-CD38 therapy. There’s been some preclinical work that has shown that patients with (11;14) myeloma have lower expression of CD38. That raises the question, does that translate to CD38 therapy being less effective in these patients?

We leveraged data from a large dataset, the Flatiron Health dataset, to look at this question. We looked at a cohort of relapsed/refractory myeloma patients, all of whom were receiving anti-CD38 therapy, and we compared outcomes between those who had (11;14) and those who didn’t have (11;14). We saw that outcomes were very similar. What you can infer from this is that, broadly speaking, CD38 therapy seems to be effective even in (11;14) myeloma, and the lower CD38 expression that you see in those cells doesn’t necessarily translate to reduced efficacy.

The way we did our analysis, we’re actually looking at the prognostic value of translocation (11;14) in those patients. It seems that in the relapsed/refractory setting, having (11;14) doesn’t seem to be a negative prognostic factor. Another interesting signal that we saw on this—though it’s super preliminary and might just be strategical noise—is that in (11;14) myeloma, amongst those patients receiving CD38 therapy, it seemed that having additional high-risk cytogenetics did not adversely impact outcomes. Now is it that the daratumumab or the isatuximab is overcoming those high-risk features? I don’t know. Again, it’s super preliminary, but that was an interesting analysis that we did. This paper will be published in Blood Cancer Journal. That was one interesting analysis that we did.

The second one that we did was a topic that’s very close to my heart, and one I think about a lot; how does progression-free survival (PFS) correlate to overall (survival) OS in multiple myeloma trials? And then, how is PFS characterized in myeloma trials? Is it ever reported if it’s a clinical progression or a biochemical progression? I think it’s important to know and differentiate between the two. In this study, which is the most updated and largest surrogacy analysis ever done for patients with multiple myeloma, we did a systematic review. We identified all randomized trials for multiple myeloma over a 15-year period, looked at those trials that reported PFS and OS, and then did a formal correlation surrogacy analysis for the hazard ratios of PFS and OS.

As things get better and better, we shouldn’t lower the standard. Things are getting better, but you also should keep up the standard for approval so that good drugs enter the market that actually benefit our patients.

Looking at the surrogacy aspect of the question, we found out if you pool all myeloma trials—and we had 41 trials, which is a pretty large surrogacy analysis—PFS does not correlate well with OS. This correlation is especially poor in newly diagnosed myeloma. Now, it’s a complex topic, and I think we have to acknowledge that the current system has worked, right? This current system, where drugs are getting approved based on PFS, has led to patients with myeloma living longer and having better therapeutic options. But I think we’re at a crossroads now where we’re trying to get measurable residual disease (MRD) established as a surrogate for PFS, and that’s pretty tricky because when PFS is not a good surrogate for OS, you don’t want to link another surrogate to PFS.

I think that’s one thing we have to be cautious about, because as things get better and better, we shouldn’t lower the standard. Things are getting better, but you also should keep up the standard for approval so that good drugs enter the market that actually benefit our patients. The other thing is that we only found one trial amongst all the trials we looked at that clearly demarcated whether a progression event was clinical or biochemical. That has immense prognostic value. We kind of need to know, are these patients on trials progressing clinically or biochemically? Is whatever agent we’re studying alleviating both, or one, and how much? I think that’s another area for improvement that we identified.

The last paper I’m discussing was about how oncology news websites report oncology news. This was inspired by speaking to a patient advocate. Last year, there was a drug in myeloma called melphalan flufenamide (melflufen), which worsened overall survival in a randomized trial, meaning that it killed more people than the control arm. But it improved progression-free survival, meaning that the duration of remission might have been longer, but people overall lived shorter.

That was very concerning study, and a patient advocate, a spouse of a person with myeloma, came up to me and said, “I’ve been looking at all of these oncology news websites, and they’re reporting this as a positive trial. They’re ignoring the OS, and they’re spinning it that PFS is better and melflufen is better for this cohort of patients.” It was very disturbing, so we studied that systematically. We looked at all oncology news reporting that came out of that event, and we found out that almost all of it was positive. That was published in Lancet Hematology. Then we wanted to systematically look at OncLive and Targeted Oncology, because those are two websites that a lot of us follow and get sent to patients and community doctors.

Over a prespecified period, we systematically analyzed all content that comes out of those websites. We found that almost none of the content is critical, and never is a conflict of interest reported. It’s expected that there’ll be some conflict of interest, but it’s never reported. I think there’s a lot of overgeneralization, a lot of hype, and a lot of spin in the content that’s reported. I’m very glad that I actually met with OncLive today, and we discussed a way to productively move forward, because we have the same goal. We want to provide good information to patients and to community doctors and to other academic doctors. It was a productive discussion, and I think something good will hopefully come.

So, that’s a summary of some of the research that I had the pleasure of being a part of at this meeting.

Oncology Data Advisor: Thank you so much. Those are two really great presentations and a very interesting study about the oncology news as well. One other question I have is, for Oncology Data Advisor, would you have any advice for the type of content that we curate or how to improve the quality of what we produce? 

There are a lot of things in oncology that, despite our best efforts, don’t succeed. I think that systematically looking back and seeing how much of your content is universally positive versus negative would be a good start.

Dr. Mohyuddin: Absolutely, that’s such a good question. I think a lot of what we studied and what we found is actually generalizable to all oncology news media websites. I think you guys are doing a great job, but moving forward, one of the solutions we discussed is that it’s important to have a balanced perspective and have some sort of critical content. If you look back at all of the content that you’ve produced, and it’s all laudatory and just positive reporting, then I think that there’s something missing. There are a lot of negative trials and a lot of trials that are underwhelming. There are a lot of things in oncology that, despite our best efforts, don’t succeed. I think that systematically looking back and seeing how much of your content is universally positive versus negative would be a good start.

We spoke about having a bunch of advisors who are independent and can help make sure that your content is critically rigorous—having some sort of a panel who you can refer to, to quickly look over your articles and make sure that they’re critical enough. Reporting conflicts of interest is obviously optional—you’re not mandated by the government—but I think it would add to the rigor of the content if you had to report conflicts of interest of the interviewees who you’re interviewing.

Then in the article that actually gets published online, have a direct link to the actual data you’re citing. Don’t make it difficult for people to find that article, because we found that sometimes it’s not reported. You have to spend a lot of time to get the source article. Then whenever possible, if you’re talking about risk reduction, include absolute risk reduction and relative risk reduction as well, because you can spin a three-week benefit of progression-free survival into 30% improvement. That’s what one study that we looked at on OncLive reported. So, try to add context. It’s difficult, but these are some early steps that can be taken to help improve the content.

Oncology Data Advisor: That’s super helpful. We’re always looking for ways to improve our content. Thanks so much for stopping by today, it was great talking with you.

Dr. Mohyuddin: Thank you again, I appreciate you.

Thank you for listening to this podcast recorded live at the 2022 ASH Annual Meeting by Oncology Data Advisor and ConveyMED. For more expert perspectives on the latest in cancer research and treatment, be sure to subscribe to the podcast at conveymed.io and OncData.com. Don’t forget to follow us on social media for news, exclusive interviews, and more!

About Dr. Mohyuddin

Manni Mohyuddin, MBBS, is an Assistant Professor in the Division of Hematology/Bone Marrow Transplant at the University of Utah Huntsman Cancer Institute, where he specializes in the treatment of multiple myeloma. His research interests focus on quality of scientific methods, drug repurposing, cost effectiveness, and evidence-based myeloma care.

For More Information

Mohyuddin GR, Chakraborty R, Calip G, et al (2022). Prognostic value of translocation 11;14 in patients with relapsed/refractory myeloma receiving anti-CD38 therapy [oral presentation]. 64th American Society of Hematology Annual Meeting. Abstract 2288.

Mohyuddin GR, Chakraborty R, Calip G, et al (2022). Prognostic value of translocation 11;14 in patients with relapsed/refractory myeloma receiving anti-CD38 therapy [oral presentation]. Blood Cancer J, 12(168). DOI:10.1038/s41408-022-00769-4

Etekal T, Koehn K, Sborov DW, et al (2022). Time to event surrogate endpoints in multiple myeloma randomized trials from 2005-2019: a surrogacy analysis. 64th American Society of Hematology Annual Meeting. Abstract 2211.

Sharma N, Wayant C, Neupane K, et al (2022). Hype, spin or accurate reporting: the quality of reporting on oncology news websites. 64th American Society of Hematology Annual Meeting. Abstract 4866.

Berger K & Mohyuddin GM (2022). Reporting of trials with possible detrimental overall survival: a patient advocate perspective. Lancet Haematol, 9(2):e94. DOI:10.1016/S2352-3026(22)00006-0

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 


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