Carfilzomib, Lenalidomide, And Dexamethasone Plus Transplant In Newly Diagnosed Multiple Myeloma

Carfilzomib, Lenalidomide, And Dexamethasone Plus Transplant In Newly Diagnosed Multiple Myeloma

In the journal Blood, on November 26, 2020, investigators reported on the phase 2 clinical trial where induction carfilzomib–lenalidomide–dexamethasone (KRd) was administered with planned autologous stem cell transplantation following 4 cycles of induction and 10 more cycles of KRd.

The combination treatment was designed for newly diagnosed multiple myeloma. The primary endpoint for investigators was the rate of stringent complete response after 8 cycles of KRd.  The predefined threshold of at least 50% was needed to support the study further.  76 patients were enrolled.  In the trial, the median age was 59, range between 40 and 76 years old.  35.5% had high risk cytogenetics.  The primary endpoint was met with a stringent complete response rate of 60% seen after 8 cycles of treatment.  The depth of response improved over time per the investigators.  

On intent to treat, the stringent complete response rate reached 76%.  Minimal residual disease negativity rate using the modified intent to treat with 70% per next generation sequencing with a 1/100,000 sensitivity.  After a median follow-up of 56 months, the 5-year progression free survival and overall survival were 72 and 84% for the ITT, 85% and 91% for the minimal residual disease negative patients and 57% and 72% for patients with high risk cytogenetics.  High risk patients who were MRD negative, had a 77% and 81% 5-year rate for progression free survival and overall survival, respectively.  There were significant grade 3 and 4 adverse events repoorted.  These included neutropenia seen in 34%, lymphopenia seen in 32% and infection seen in 22%.  A small but important cardiac risk was seen with 3%.  No grade 3 or 4 peripheral neuropathy was documented.  

The authors concluded “patients with newly diagnosed multiple myeloma treated with KRd with autologous stem cell transplantation achieved high rates of stringent complete response and minimal residual disease negative disease at the end of KRD consolidation.  Extended KRd maintenance after consolidation contributed to deepening of response is unlikely to prolong progression free survival and overall survival.  Safety and tolerability were acceptable.”