What cancer types does daratumumab (Darzalex) treat?

Daratumumab Treatment Indications in Multiple Myeloma

Daratumumab (Darzalex) is FDA-approved and guideline-recommended exclusively for the treatment of multiple myeloma across multiple clinical settings, including newly diagnosed disease (both transplant-eligible and ineligible patients), relapsed/refractory disease, and as monotherapy in heavily pretreated patients. 1

FDA-Approved Indications for Multiple Myeloma

Daratumumab is indicated for adult patients with multiple myeloma in the following specific combinations and settings 1:

Newly Diagnosed Multiple Myeloma – Transplant-Ineligible Patients

• In combination with lenalidomide and dexamethasone (D-Rd) for newly diagnosed patients who are ineligible for autologous stem cell transplant 1
• In combination with bortezomib, melphalan, and prednisone (D-VMP) for newly diagnosed patients who are ineligible for autologous stem cell transplant 1

Newly Diagnosed Multiple Myeloma – Transplant-Eligible Patients

• In combination with bortezomib, thalidomide, and dexamethasone (D-VTd) for newly diagnosed patients who are eligible for autologous stem cell transplant 1

Relapsed or Refractory Multiple Myeloma

• In combination with lenalidomide and dexamethasone in patients who have received at least one prior therapy 1
• In combination with bortezomib and dexamethasone (DVd) in patients who have received at least one prior therapy 1
• In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy 1
• In combination with pomalidomide and dexamethasone (DPd) in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor 1

Heavily Pretreated Multiple Myeloma

• As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent 1

Guideline-Supported Treatment Positioning

First-Line Therapy

The NCCN guidelines designate daratumumab-based triplet regimens as Category 1 preferred options for newly diagnosed multiple myeloma 2, 3:

• D-Rd (daratumumab/lenalidomide/dexamethasone) is the preferred regimen for transplant-ineligible patients, demonstrating superior progression-free survival (70.6% vs 55.6% at 30 months) compared to lenalidomide/dexamethasone alone 3
• D-VMP achieved an 18-month PFS of 71.6% versus 50.2% with VMP alone in the ALCYONE trial 2, 4
• Dara-VTd for transplant-eligible patients improves stringent complete response rates (39% vs 26% at day 100 post-transplant) and PFS versus VTd alone in the CASSIOPEIA trial 2, 3

Relapsed/Refractory Disease

NCCN guidelines list daratumumab-based combinations as Category 1 preferred options for relapsed/refractory multiple myeloma 2, 4:

• DRd is the primary choice for lenalidomide-sensitive first relapse, delivering a median PFS of 45 months with the greatest reduction in progression risk (HR 0.31, P<0.0001) in the POLLUX trial 2, 3, 4
• DVd is the preferred regimen for lenalidomide-refractory first relapse, with a 12-month PFS rate of 60.7% versus 26.9% (HR 0.39, P<0.001) in the CASTOR trial 2, 4, 5
• Patients with only one prior line of therapy showed exceptional benefit, with median PFS of 27.0 versus 7.9 months (HR 0.22, P<0.0001) when receiving daratumumab-based regimens 2, 4

Heavily Pretreated Patients

• Daratumumab monotherapy is FDA-approved for patients who have received at least three prior therapies, achieving an overall response rate of approximately 29-30% with a median response duration of 7.4 months 2, 4, 6

Non-Multiple Myeloma Indication

Light Chain (AL) Amyloidosis

While not the primary focus of the question, daratumumab plus CyBorD (cyclophosphamide/bortezomib/dexamethasone) received FDA approval for newly diagnosed AL amyloidosis based on the phase III ANDROMEDA study, which demonstrated substantially improved hematologic complete response rates and survival free from major organ deterioration 7. This represents the first approved therapy specifically for AL amyloidosis 7.

Clinical Efficacy Across Settings

Daratumumab demonstrates consistent efficacy across all multiple myeloma treatment settings 8:

• Newly diagnosed transplant-ineligible patients: Overall survival benefit demonstrated in ALCYONE and MAIA trials 8
• Newly diagnosed transplant-eligible patients: Improved depth of response in CASSIOPEIA and GRIFFIN trials 8
• Relapsed/refractory disease: Consistent improvement in progression-free survival and response rates in POLLUX, CASTOR, APOLLO, and CANDOR trials 8

Important Clinical Considerations

Daratumumab is administered exclusively for plasma cell disorders (multiple myeloma and AL amyloidosis) and has no approved indications for other cancer types 1, 7. The drug targets CD38, which is highly expressed on malignant plasma cells, making it specifically effective for these plasma cell dyscrasias 2, 6.