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Using KRd Regimen to Treat Plasma Cell Leukemia
Posted: Nov 30, 2023
Using KRd Regimen to Treat Plasma Cell Leukemia  image

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:

 

Younger patients (18-65 years)

Older patients (65 years)

Induction

4 cycles of 28 days

·       Kyprolis at 36 mg/m² on days 1, 2, 8, 9, 15,16

·       Revlimid a 25 mg on days 1-21

·       Dexamethasone @ 20 mg on days 1, 2, 8, 9, 15,16 

8 cycles with a regimen the same as for younger patients

Stem cell transplants

Tandem auto-SCT (i.e., two back-to-back auto-SCT’s)

 

Or

 

Auto-SCT followed by tandem-SCT (see note 1 below and note 2 below)

 

None

Consolidation

4 cycles of 28 days, same as induction

None

Maintenance

12 cycles of 28 days

·       Kyprolis at 27 mg/m² on days 1, 2. 15, 16

·       Revlimid at 10 mg on days 1-21

 

Cycle 13 until disease progression

·       Kyprolis at 56 mg/m² on days 1, 15

·       Revlimid 10 mg days 1-21

Same as for younger patients

Progression-free survival

15.5 months

13.8 months

Overall Survival

28.4 months

24.8 months

Early mortality  at 6 months

8.3 %

16 %

Note 1

There is recent medical literature that for pPCL, tandem ASCT (autologous stem cell transplant) has improved outcomes in pPCL patients who achieve CR (complete response) after induction (and prior to the first transplant) whereas auto-allo-SCT may be more appropriate for patients who did not achieve CR after induction [see article].

Note 2

Patients who have received auto-allo SCTs skip the consolidation phase of treatment and go right to maintenance.

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. 

The author Paul Kleutghen

about the author
Paul Kleutghen

I am a patient diagnosed in 2014 with primary plasma cell leukemia (pPCL), a rare and aggressive variant of multiple myeloma and have been very fortunate to find successful treatment at the division of Cellular Therapy at the Duke University Cancer Institute. My wife, Vicki, and I have two adult children and two grandsons who are the ‘lights of our lives’. Successful treatment has allowed Vicki and I to do what we love best : traveling the world, albeit it with some extra precautions to keep infections away. My career in the pharmaceutical industry has given me insights that I am currently putting to use as an advocate to lower drug pricing, especially prices for anti-cancer drugs. I am a firm believer that staying mentally active, physically fit, compliant to our treatment regimen and taking an active interest in our disease are keys to successful treatment outcomes.

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