Increasing Daratumumab Frequency As a Way to Restore Responses- a Retrospective Case Study

Introduction:

Multiple Myeloma (MM) remains difficult to treat despite significant advances in treatment options. Daratumumab (dara) as a single-agent or in combination with other treatments has considerable efficacy even among patients with highly-refractory disease. However, nearly all patients will fail dara. Dara frequency decreases throughout the treatment, from weekly eventually to monthly dosing, which may in part contribute to relapse. It has been hypothesized that increasing the frequency of dara may help restore responses in patients progressing on dara, but little data exists.

Methods:

In this retrospective case study, we identified 5 patients from our clinical database who received standard dara (weekly for 2 cycles, every other week for 4 cycles, then monthly thereafter) as a single agent or in combination, who had frequency re-escalated at relapse in attempt to recapture response.

Results:

Patient 1 is a 67 yo male with quad-refractory MM who received single-agent dara. He had a PR following 1 cycle but disease plateaued, ultimately progressing with rising M-protein following cycle 7 of treatment. Dara frequency was re-escalated to once weekly and the patient once again obtained a PR following the first cycle. The patient received 2 additional cycles at which time he had further evidence of PD and was switched to alternative treatment.

Patient 2 is a 68 yo female with quad-refractory MM who received single-agent dara. She had a PR following 1 cycle but disease plateaued, ultimately progressing with rising free-light chains following cycle 12 of treatment. Dara frequency was re-escalated to once every other week. The patient had a mild reduction free-light chains (not meeting PR) and went on to receive 8 additional cycles before having further evidence of PD and switching to supportive care only.

Patient 3 is a 73 yo male with refractory MM who received dara in combination pomalidomide (pom) and dexamethasone (dex). The patient had previously progressed on pom/dex. He had a PR following 2 cycles but disease plateaued, ultimately progressing with rising free-light chains following cycle 8 of treatment. Dara frequency was re-escalated to once weekly. The patient had a mild reduction in free-light chains (not meeting PR) and went on to receive 5 additional cycles before having further evidence of PD and switching to alternative treatment.

Patient 4 is a 68 yo male with refractory MM who received single-agent dara. He had a PR following 1 cycle, and a VGPR following cycle 3. The patient later progressed following 14 cycles with rising M-protein and new lesion requiring XRT. Dara frequency was re-escalated to once weekly. The patient had a mild reduction M-protein (not meeting PR) and went on to receive 8 additional cycles before having further evidence of PD and switching to alternative treatment.

Patient 5 is a 69 yo female with refractory MM who received dara/pom/dex. She was previously naïve to pom. The patient initially had stable disease but progressed with increasing free-light chains following cycle 6. Dara frequency was re-escalated to once weekly. The patients free-light chains returned to baseline levels and she went on to receive an additional 5 cycles before having further evidence of PD and switching to alternative treatment.

Conclusion:

Increasing dara frequency, can result in stabilization or improvement of myeloma disease markers in patients who were previously relapsing. This strategy may be clinically beneficial to patients who are showing signs of early biochemical progression but are otherwise doing well. Prospective trials are warranted to further evaluate this approach.

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