The long awaited interim results of efficacy and toxicity from the phase 3 ENDURANCE trial (E1A11) for Newly Diagnosed Multiple Myeloma failed to show a superior Progression Free Survival (PFS) with Kyprolis, Revlimid and Dexamethasone (KRd) when compared to Velcade, Revlimid and Dexamethasone (VRd), the current standard of care for newly diagnosed multiple myeloma patients.
These results are important because initial therapy has the greatest impact on patient outcomes in multiple myeloma.
This trial was also designed to examine the effect on overall survival of the indefinite use of lenalidomide maintenance vs. a fixed duration of 2 years.
This ECOG-ACRIN (Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network) study was designed based on results from previous smaller Phase II studies that suggested the second generation proteasome inhibitor Carfilzomib (Kyprolis) was more effective than Bortezomib (Velcade). Although a higher incidence of greater than Very Good Partial Response (VGPR) was seen with KRd over VRd (73.8% vs 64.7%) p=0.002, this did not result in an improved Progression Free Survival (PFS).
After Dr. Shaji Kumar, the lead investigator, presented this trial, Dr. Jesus Berdeja did a brief presentation highlighting additional data. He also points out that we now have two equivalent proteasome inhibitors to choose from.
The trial was looking at two key end points:
Overall survival for the second randomization of Lenalidomide maintenance indefinitely vs. fixed duration of 2 years.
As of the second of three planned interim analysis, data cut-off January 7, 2020 the results were as follows:
|Median Progression Free Survival||34.6 months||34.4 months|
|Overall Survival (with 95% confidence interval)||86%||84%|
* PFS treatment hazard ratio KRd/Vrd was 1.04 (95%CI, 0.83-1.31); p=0.74.
|Over Grade 3 toxicity rates||41%||48%|
|Combined cardio, pulmonary and renal||5%||16%|
|Patients taken off trial to use other MM therapies||18%||14%|
|Patients taken off trial because of severity of side effects||17%||9%|
|Patients taken off trial because of disease progression||6%||4%|
|Patients who withdrew from the trial||7%||4%|
Dr. Shaji Kumar concluded that these results prove that VRd should remain the standard of care and that VRd should be the backbone upon which quadruplet therapies should be designed.
Dr. Jesus Berdeja pointed out two important differences in the regimens given that they are of equal efficacy:
Dr. Berdeja concluded that comorbidities and toxicity profiles should guide the choice for each patient.
As with all things myeloma there has been a great deal of conversation among myeloma specialists on Twitter about these results. Some interpret this as VRd is not better than KRd. Some see it as we have a choice, and some question certain aspects of the trial design.
However you the patient are now armed with info to discuss this with your myeloma specialist and decide together what's best for you!
about the author
Bonnie is a Myeloma Coach and the caregiver for her husband with Multiple Myeloma. They live at the foot of the Blue Ridge Mountains in Afton, VA with their 2 dogs and 2 cats.