Before ASCO even got started the first week of June, our lifestyle columnist and my good friend, Danny Parker, alerted me to an incredibly important abstract that we both knew would get lost among all of the hype. A retrospective study conducted by myeloma specialists at Mayo Clinic, it revealed some groundbreaking overall survival (OS) news.
At the time, I felt it might be the most groundbreaking report about myeloma coming out of Chicago; yet the authors weren’t even invited to speak.
Danny has kindly written a review for us. I’m happy to share it with you now:
I wanted to call your attention, and that of your readers, to an important study done by the Mayo Clinic that was presented as a poster at the ASCO 2013 meeting. You know I have been eager to share this one.
“The Beneficial Effect of Complete Response and Type of Therapy in Multiple Myeloma”
This is Shivlal Pandey et al.
The study comprises a large sample of patients– 462 who had achieved a complete response (CR). The patients were also followed for a long time– twenty years. The CRs were achieved by different means for the large number of patients. The results are based on data taken on patients treated at Mayo Clinic between 1991 and 2011 with good and consistent data quality.
It has long been known that achievement of a CR has been a bellwether for better outcomes with myeloma. However, this study for the first time allows us some insight into the interaction of achieving CR with the accelerated development of novel agents and improved treatments. Were there differences?
A notable highlight of Dr. Pandey’s study was that the statistics indicated a typical 10.7 Yr overall survival (OS) survival from diagnosis for patients if they can reach CR. A key finding was that this 10 year OS was true for patients regardless whether achieved by stem cell transplant (SCT) or novel agents. Also, digging into the data in the sample, one can see that the group receiving lenalidomide (Revlimid) plus Bortezomib (Velcade) who reached CR, had not reached the median OS at the end of the study– the treatment was too new! The study also found that while hi-risk patients showed poorer outcomes, the cohort showed progress at longer OS for this group than in the past. A sub-sample of the patients achieve stringent complete response (sCR) with these showing even longer indicators for survival. The evaluation estimated the 15 year survival for patients achieving CR at 40%.
Of course, the time to progression (TTP) after CR was shorter– about 5-6 years, so this means that we often struggle with therapy after relapse. But even this period is fairly long– we often survive for five years more. Not a rosy picture, but still much better than earlier conventional wisdom from the 90s where overall survival was only this long.
The other BIG thing about this is that Velcade only arrived on the scene in 2003 and lenalidomide in 2006; thus, this study is still looking in the rear view mirror and patients are likely surviving longer now. Thus, this showcases one of the real limitations of statistics on treating a disease where progress in treatment is rapid. We are always looking backwards into the past to learn about the present and anticipate the future.
Still, given medical progress over the last decade, it is hard to understate the significance of this study. With the latest novel agents, such as Carfilzomib and Pomalidomide– and the game changing CD38 monoclonal antibodies such Daratumumab on the horizon– it’s logical to expect better things in the future. Moreover, with the powerful new additions to our arsenal of treatments, many myeloma patients today are reaching CR either with, or without a SCT.
Finally, in recent years, we are learning how to better gauge the depth of remissions through flow cytometry and DNA sequencing. Such approaches will allow our doctors to better evaluate the level of minimal residual disease (MRD) so that we can potentially reach the end-result we’re all looking for: cure.
While having myeloma is certainly a difficult challenge and many of us are still suffering, prospects have never been brighter for patients than they are now. So, hats off to the doctors and medical research establishment for helping us to live longer, and more productive lives.
Here is a PDF of the poster presentation:
Beneficial effect of complete response and type of therapy in multiple myeloma
Shivlal Pandey, S. Vincent Rajkumar, Angela Dispenzieri, Martha Lacy, Morie Gertz, Francis Buadi, David Dingli, Suzanne R. Hayman, Stephen J. Russell, John Anthony Lust, Steven R. Zeldenrust, Prashant Kapoor, Arleigh Robertson McCurdy, Robert A. Kyle, Shaji Kumar; Mayo Clinic, Rochester, MN
J Clin Oncol 31, 2013 (suppl; abstr 8541)
Background: Achievement of a complete response (CR) to treatment is an important predictor of outcome for patients (pts) with myeloma (MM). The goal of the current study was to assess whether the treatment that resulted in CR has any impact on the outcomes. Methods: We identified 462 pts with MM, who fulfilled the IMWG criteria for CR, seen at Mayo Clinic between 1991 and 2011. The treatment was classified into groups by the regimen that led to CR (Table), and also based on whether an autologous stem cell transplant (ASCT) was part of the regimen. The remaining 21 pts had a variety of regimens and are not included in the Table. Results: The median age at diagnosis was 58.5 yrs (27.1–82.3 yrs) with 56% males. The overall survival (OS) from diagnosis for the entire cohort was 10.7 yrs (95% CI; 9.3, NR). The median interval from diagnosis to the recorded CR was 10.3 mos (range 1- 170), with 272 (58.4%) and 385 (82.7%) obtaining a CR in <12 mos and <24 months from diagnosis. We first compared the outcomes based on whether ASCT was part of the regimen; 328 had an ASCT while 117 pts received only chemotherapy. Median time to progression (TTP) following a CR was 5.1 yrs for the ASCT group compared with 5.5 yrs for the rest (P=0.3). Median OS from CR was 9.1 yrs for the ASCT group and 7.5 yrs for the rest (P=0.5) and OS from diagnosis was 10.1 yrs for the ASCT group and 12.6 for the rest (P=0.5). Examining the outcomes based on the regimen utilized showed that the TTP and OS from CR as well as OS from diagnosis were similar for all the groups (Table). Among pts who had a CR within a year of diagnosis, there were no differences in terms of the TTP or OS from the onset of CR or from diagnosis between the ASCT vs. chemotherapy groups or between the different regimens (P=NS for all comparisons). Conclusions: The current study highlights an important message regarding CR in MM. The results suggest that the prognostic value of CR is independent of the nature of therapy, and likely reflects the contribution of disease biology to obtaining a CR.
|Median from CR (yrs)||Median from diagnosis (yrs)|
|Lenalidomide + bortezomib based||41||3.5||NR||NR|
Encouraging, don’t you think? Imagine how good these numbers will look after all of the new myeloma therapy options kick-in! Time for doctors to start presenting more optimistic median life expectancy numbers to newly diagnosed patients.
Feel good and keep smiling! Pat