Immunotherapy for the Treatment of Multiple Myeloma

Dara is FDA-approved and the panel recommends its use in the following settings:

• In combination with lenalidomide and dexamethasone (D-Rd)in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with RRMM who have received at least one prior therapy.

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

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

• In combination with bortezomib and dexamethasone (D-Vd) in patients who have received at least one prior therapy.

• In combination with pomalidomide and dexamethasone (D-Pd)in patients who have received at least two prior therapies including lenalidomide and a PI.

• As monotherapy, in patients who have received at least three prior lines of therapy including a PI and an IMiD or who are double-refractory to a PI and an IMiD.

Other combinations in newly diagnosed patients:

• Based on emerging data (e.g. from the Griffin trial37), the panel was comfortable recommending D-VRd as one possible induction regimen option in newly diagnosed patients who are eligible for autologous stem cell transplant.

• A consensus could not be reached regarding the use of dara in combination with carfilzomib, lenalidomide and dexamethasone (D-KRd) in newly diagnosed patients who are eligible for autologous stem cell transplant.

Other combinations in RRMM:

• KdD is recommended for patients with RRMM in the USA that are refractory to immunomodulatory drugs and bortezomib, based on emerging data from the CANDOR trial.

Until further phase III data become available, a consensus could not be reached to recommend that dara is the definitive choice for patients with high-risk cytogenetics, particularly in the frontline setting.

Standard premedications as suggested below may be used to mitigate IRRs:

• Dexamethasone, 20 mg intravenous (IV) (for dara monotherapy methylprednisolone, 100 mg is preferred).

• Acetaminophen, 650–1000 mg oral.

• Diphenhydramine, 25–50 mg oral or intravenous.

• Montelukast, 10 mg, orally dissolving tablet (ODT) preferred, prior to first infusion.

After cycle 2, steroids may be omitted if the patient has tolerated dara without IRRs.

For patients with severe IRRs during dose or a history of respiratory comorbidities, oral corticosteroids (≤20 mg methylprednisolone or equivalent intermediate-acting or long-acting corticosteroid) should be administered per the prescribing label on each of the 2 days following dara infusions.

Short-acting and long-acting bronchodilators and inhaled corticosteroids may be considered for patients with a long history of chronic obstructive pulmonary disease (COPD).

The panel felt that the new subcutaneous formulation will provide a convenient option for patients.

Although patients with renal failure, patients with COPD and patients with plasma cell leukemia are commonly excluded from clinical trials, the panel felt that these populations may safely be treated with dara.

Before administering dara, patients should be tested for hepatitis B, given the potential risk of viral reactivation.

For patients with no known hepatitis B exposure history, serum tests should be performed for HepBcAb, HepBsAb, and HepBsAg. In cases with evidence of hepatitis B exposure, a PCR test for hepatitis B genomes is recommended. For patients with positive serum tests for HepBcAb, entacavir should be considered.

Prophylactic acyclovir should be administered to patients receiving dara.

Response to dara should be monitored according to institutional protocols, most of which assay MM labs monthly. In patients with IgG kappa myeloma, serologic determination of CR can be confounded by the presence of dara.

In the presence of a measurable M-spike, dara will have a minimal effect on disease measurement. When patients reach undetectable levels, however, mass spectrometry or other antibody interference testing methods should be considered.

A consensus could not be reached to recommend retreatment with dara in patients relapsing on monthly dosing.

Patients on dara should receive seasonal influenza vaccines.

To manage infections following treatment, intravenous IgG (IVIG) should be administered according to established institutional criteria, which are not specific to dara.