ASCO 2023: A New Induction Therapy for Newly Diagnosed Myeloma

While no one would wish myeloma upon someone else, there has never been a better time to be a myeloma patient. Research continues to move the field forward, evident at the recent 2023 ASCO Conference. 

At one of the many ASCO sessions hosted within the last week, the following oral abstract was presented by Dr. Stefan Knop, MD, of University Hospital of Würzburg. Their study proposed a new standard of care induction therapy for multiple myeloma patients (also known as E-KRd) by introducing elotuzumab (EMPLICITI) to the already successful regimen of KRd, namely Kyprolis (carfilzomib), REVLIMID (lenalidomide) and dexamethasone.

Could this be the new standard of care induction therapy for newly diagnosed myeloma patients? Read more about this intriguing trial below to learn more. 

What question was the clinical trial trying to answer? What phase was this trial in? 

Investigators sought to examin the role of Elotuzumab in newly diagnosed multiple myeloma treatment. 
The first co-primary endpoint was to examine if Elotuzumab combined with KRd during induction yields better response for patients than KRd induction.

This was a Phase III (3) trial, meaning that the new drug regimen (E-KRd) was being compared to the standard of care (KRd). 

How many people participated and what were the qualifications?

579 pts (574 of whom received treatment). 
The qualifications included: must be transplant eligible, newly diagnosed with multiple myeloma, and no older than 70 years of age. 

How long did the study last and when was it completed?

This study is ongoing, and is estimated to be completed August 2029. However, the results from restaging after induction and assessing VGPR (very good partial response) and MRD (minimal residual disease) negativity status have concluded. 

What were the final results?

Responses:

• MRD (minimal residual disease) negativity and a response greater than or equal to VGPR (very good partial response) was achieved in 145 of patients who received the E-KRd (49.8%) regimen and in 102 (35.4%) of those who received current standard-of-care KRd, respectively (p=.0005). 

Health Concerns:

• Treatment-emergent adverse events (TEAEs) of > grade 3 occured in 212 (72.9%) of E-KRd versus 177 (62.5%) of KRd patients.
• Febrile neutropenia occured in 26 (6.4%) E-KRd versus 14 (4.9%) KRd patients.
• Grade 3/4 thrombocytopenia occured in 36 (12.4%) E-KRd and 30 (10.6%) KRd patients.
• Pneumonia occurred in 24 E-KRd (8.2%) and 18 KRd (6.4%) patients.
• Grade 3/4 cardiac events occurred in 16 E-KRd (5.5%) and of grades 3 to 5 in 16 (5.7%) of KRd patients.
• COVID-19 infections with one grade 5 event each occured in 12 E-KRd (4%) and 9 KRd (3.2%) patients (0.3% and 0.4%, respectively).
• Three pts on E-KRd (1.0%) versus 7 on KRd (2.5%) died on induction due to infections (N=3), MM progression (2), AML (1), a cardiac event (N=1), other (N=3).

Why is this important to patients in today’s myeloma?

Results from this study can aid patients and physicians in deciding whether to undergo KRd induction or E-KRd induction therapy based on their difference in the rates of achieved desired response (MRD negativity and > VGPR) and also based on the difference in the rates of acquired side effects or other health concerns.

We would like to thank the following specialists and researchers who made this trial possible, along with the patients who participated and their supportive caregivers. 

Stefan Knop, Thomas Stuebig, Miriam Kull, Richard Greil, Normann Steiner, Florian Bassermann, Axel Nogai, Marie von Lilienfeld-Toal, Snjezana Janjetovic, Karolin Trautmann-Grill, Max Bittrich, Monika Martha Engelhardt, Anette Hoferer, Sebastian Theurich, Mascha Binder, Niklas Zojer, Heinz A. Duerk, Monika Brueggemann, Swantje Held, Hermann Einsele