Can Daratumumab (Darzalex) (RVd) regimen be used after patients have been on Thalidomide (Thalomid)?

From the Guidelines

Yes, Daratumumab in combination with Lenalidomide, Bortezomib, and Dexamethasone (Dara-RVd) can be used in patients who have previously been on thalidomide, as thalidomide and lenalidomide have different side effect profiles and mechanisms of action 1. When switching from thalidomide to a Dara-RVd regimen, physicians should monitor for potential cumulative toxicities, particularly peripheral neuropathy which can occur with both thalidomide and bortezomib.

Key Considerations

• A typical Dara-RVd regimen includes daratumumab 16 mg/kg IV, lenalidomide 25 mg orally on days 1-14, bortezomib 1.3 mg/m² subcutaneously on days 1,4,8, and 11, and dexamethasone 20-40 mg weekly, administered in 21-day cycles.
• Patients should have a washout period of at least 2 weeks after discontinuing thalidomide before starting lenalidomide to minimize overlapping toxicities.
• The rationale for this approach is that daratumumab targets CD38 on myeloma cells while lenalidomide enhances immune function through different pathways than thalidomide, potentially overcoming resistance that may have developed to the previous therapy.

Evidence Support

• The CASTOR trial demonstrated that the addition of daratumumab to bortezomib and dexamethasone improved overall response rate, depth of response, and PFS in patients with relapsed multiple myeloma 1.
• The POLLUX study showed that the addition of daratumumab to lenalidomide and dexamethasone improved overall response rate, depth of response, and PFS in patients with relapsed multiple myeloma 1.

Clinical Implications

• Daratumumab-based regimens, such as Dara-RVd, offer a viable treatment option for patients who have previously been on thalidomide.
• Physicians should carefully monitor patients for potential toxicities and adjust treatment accordingly.
• The use of daratumumab in combination with lenalidomide, bortezomib, and dexamethasone can provide a clinically meaningful benefit in terms of response rate and PFS in patients with relapsed multiple myeloma.

From the FDA Drug Label

In Combination with Bortezomib, Thalidomide and Dexamethasone (D-VTd) The DARZALEX dosing schedule in Table 3 is for combination therapy with bortezomib, thalidomide, and dexamethasone (4-week cycle regimen) for patients with newly diagnosed multiple myeloma eligible for ASCT

The DARZALEX (Daratumumab) regimen can be used in combination with Bortezomib, Thalidomide, and Dexamethasone (D-VTd) for patients with newly diagnosed multiple myeloma eligible for ASCT. However, there is no direct information in the provided drug labels that specifically addresses the use of the RVd (Daratumumab, Bortezomib, and Dexamethasone) regimen after patients have been on Thalidomide (Thalomid).

• The labels provide dosing schedules for various combinations, including D-VTd, but do not explicitly discuss switching from or after Thalidomide treatment.
• Key considerations for using Daratumumab include its administration, dosing, and potential for infusion-related reactions, but the labels do not directly answer the question regarding sequential use after Thalidomide. 2 2

From the Research

Daratumumab (Darzalex) Regimen After Thalidomide (Thalomid)

• The provided studies do not directly address the use of the Daratumumab (Darzalex) (RVd) regimen after patients have been on Thalidomide (Thalomid) 3, 4, 5, 6, 7.
• However, the studies suggest that Daratumumab can be used in combination with lenalidomide, bortezomib, and dexamethasone (RVd) for newly diagnosed multiple myeloma, and that this combination improves progression-free survival and overall response rates compared to RVd alone 3, 4, 5.
• Additionally, the studies indicate that Daratumumab can be used as part of a first-line regimen, and that this approach may be cost-effective and improve outcomes for transplant-eligible patients with newly diagnosed multiple myeloma 6, 7.
• There is no direct evidence to suggest that prior use of Thalidomide would preclude the use of the Daratumumab (Darzalex) (RVd) regimen, but this would depend on individual patient factors and the specific treatment protocol being used.

Key Findings

• Daratumumab improves progression-free survival and overall response rates when used in combination with RVd for newly diagnosed multiple myeloma 3, 4, 5.
• Daratumumab may be used as part of a first-line regimen, and this approach may be cost-effective and improve outcomes for transplant-eligible patients with newly diagnosed multiple myeloma 6, 7.
• The safety profile of Daratumumab in combination with RVd is consistent with the known safety profiles of the individual components, with common adverse events including neutropenia, thrombocytopenia, and anemia 3, 4, 5.