Using KRd Regimen to Treat Plasma Cell Leukemia

Those of us with pPCL are used to having the opening line of a medical article regarding our myeloma variant read similarly to the opener of a recent article published in the journal The Lancet Oncology, “Primary plasma cell leukemia is an aggressive plasma cell malignancy with a poor prognosis and high early mortality due to disease-related and therapy-related complications and accounts for approximately 1–2% of patients with multiple myeloma [300 – 600 newly diagnosed patients per year].”

The article mentions that “Based on historical treatment data in primary plasma cell leukemia, median progression-free survival was approximately 9 months among younger patients and 6.5 months among older patients.”

This was indeed quite true 10 years ago, though with the more recent introduction and clinical use of the more “modern” drugs, things have been looking up for pPCL patients.

For example, a 2019 report published in ACS Journals references a study that indicates, “In a phase 2 trial presented by the Intergroup Francophone du Myelome (IFM), ASCT-eligible patients with pPCL received a bortezomib-based induction regimen followed by tandem SCT; combined bortezomib, lenalidomide, and dexamethasone (VRD) consolidation; and lenalidomide maintenance. This approach resulted in a median OS of 36 months.”

Over the past few years, we have also seen the introduction of the quadruplet approach Darzalex-RVd that may further improve outcomes [though data for pPCL are still immature for publication].

The Lancet Oncology article referenced above summarizes retrospective outcomes pooled from centers in seven European countries using a triplet of Kyprolis-Revlimid- dexamethasone (KRd).

A total of 61 patients were followed over a period of several years. These patients were stratified into two groups: 36 young patients (18-65 years) and 25 older patients (> 65 years). Please note that pPCL is more prevalent in younger patients than myeloma.

Treatment regimens can be summarized as follows:

These results are better than the historical outcomes that have been reported in the past, PRIOR to the advent of the more novel treatments currently available.

The authors however, conclude, “Despite the impressive improvement in survival outcomes among all patients with [myeloma], especially with the increasing use of [stem cell transplant] and the incorporation of novel agents into the induction and maintenance phases, the survival improvement observed in patients with pPCL still is not on a par with that attained in patients with [myeloma]”.

As a bystander with “skin in the game”, I am not overwhelmed by these reported outcomes, considering that a report published in 2018 using an RV (Revlimid Velcade) induction-consolidation regimen, with a single auto-SCT and with RVd maintenance, Progression Free Survival clocked in at 27 months and Overall Survival clocked in at a median of 38 months.