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Major toxicities of selected treatment regimens used for relapsed multiple myeloma

Regimen	Major toxicities	Adjunctives	Clinical use	Other
Options for initial relapse
Daratumumab, lenalidomide, dexamethasone (DRd)	Acute or delayed hypersensitivity reaction, opportunistic infections, diarrhea, fatigue.	Prophylaxis for infusion reactions; antiviral prophylaxis; thromboprophylaxis.	Preferred for patients relapsing off therapy or while on small doses of single agent lenalidomide or on bortezomib maintenance.	Can interfere with cross-matching and red blood cell antibody screening.
Daratumumab, bortezomib, dexamethasone (DVd)	Peripheral neuropathy, transient cytopenias, acute or delayed hypersensitivity reaction, fatigue, nausea.	Prophylaxis for infusion reactions; antiviral prophylaxis.	Preferred if refractory to full doses of lenalidomide or refractory to a lenalidomide containing triplet.	Can interfere with cross-matching and red blood cell antibody screening.
Daratumumab, carfilzomib, dexamethasone (DKd)	Hypersensitivity reaction, transient cytopenias, fatigue, diarrhea, hypokalemia, hypertension, dyspnea, serious cardiac dysfunction (approximately 5%).	Prophylaxis for infusion reactions; antiviral prophylaxis; thromboprophylaxis.	Option for patients refractory to both bortezomib and lenalidomide.	Can interfere with cross-matching and red blood cell antibody screening.
Isatuximab, carfilzomib, dexamethasone	Hypersensitivity reaction, transient cytopenias, respiratory infections, fatigue, diarrhea, hypertension, serious cardiac dysfunction.	Prophylaxis for infusion reactions; antiviral prophylaxis.	Option for patients refractory to both bortezomib and lenalidomide.	Can interfere with cross-matching and red blood cell antibody screening.
Bortezomib, lenalidomide, dexamethasone (VRd)	Peripheral neuropathy, transient cytopenias, fatigue, gastrointestinal distress.	Thromboprophylaxis; antiviral prophylaxis.	May be preferred for patients relapsing off therapy or on lenalidomide maintenance.	Subcutaneous, once-weekly dosing of bortezomib decreases toxicity.
Bortezomib, cyclophosphamide, dexamethasone (VCD)	Peripheral neuropathy, transient cytopenias.	Antiviral prophylaxis; PCP prophylaxis.	May be preferred for patients relapsing while off therapy or on lenalidomide maintenance.	Subcutaneous, once-weekly dosing of bortezomib decreases toxicity.
Carfilzomib, lenalidomide, dexamethasone (KRd)	Gastrointestinal distress, transient cytopenias, fatigue, hypokalemia, hypertension, dyspnea, serious cardiac dysfunction (approximately 5%).	Thromboprophylaxis; antiviral prophylaxis.	May be preferred for more aggressive relapse in fit patients.	More cumbersome than weekly schedule of bortezomib- or ixazomib-based regimens.
Carfilzomib, pomalidomide, dexamethasone (off-label)	Transient cytopenias, fatigue, hypokalemia, hypertension, dyspnea, potentially severe diarrhea, serious cardiac dysfunction (approximately 5%).	Thromboprophylaxis; antiviral prophylaxis.	May be preferred for patients with aggressive disease relapsing on standard dose lenalidomide.
Bortezomib, pomalidomide, dexamethasone (off-label)	Peripheral neuropathy, thrombocytopenia, lymphopenia, potentially severe diarrhea, asthenia/fatigue, peripheral neuropathy.	Thromboprophylaxis; antiviral prophylaxis.	May be preferred for patients relapsing on standard dose lenalidomide.
Ixazomib, lenalidomide, dexamethasone (IRd)	Diarrhea, constipation, nausea, vomiting, thrombocytopenia, peripheral neuropathy, peripheral edema, and back pain.	Thromboprophylaxis; antiviral prophylaxis.	May be preferred for frail patients or those with a clinically indolent relapse.	Oral regimen.
Elotuzumab, lenalidomide, dexamethasone	Acute or delayed hypersensitivity reaction, opportunistic infections, hepatic dysfunction, fatigue.	Prophylaxis for infusion reactions; antiviral prophylaxis; thromboprophylaxis.	May be preferred for frail patients or those with a clinically indolent relapse.
Options for multiply relapsed disease: Includes regimens above that have not yet been used
Daratumumab, pomalidomide, dexamethasone	Hypersensitivity reaction, thrombocytopenia, lymphopenia, potentially severe diarrhea, asthenia/fatigue, peripheral neuropathy.	Prophylaxis for infusion reactions; antiviral prophylaxis; thromboprophylaxis.	Reserved for patients who have had at least two prior regimens, including lenalidomide and a proteasome inhibitor.	Can interfere with cross-matching and red blood cell antibody screening.
Isatuximab, pomalidomide, dexamethasone	Hypersensitivity reaction, thrombocytopenia, lymphopenia, potentially severe diarrhea, asthenia/fatigue, peripheral neuropathy.	Prophylaxis for infusion reactions; antiviral prophylaxis; thromboprophylaxis.	Reserved for patients who have had at least two prior regimens, including lenalidomide and a proteasome inhibitor.	Can interfere with cross-matching and red blood cell antibody screening.
Elotuzumab, pomalidomide, dexamethasone	Acute or delayed hypersensitivity reaction, opportunistic infections, hepatic dysfunction, thrombocytopenia, lymphopenia, potentially severe diarrhea, asthenia/fatigue.	Prophylaxis for infusion reactions; thromboprophylaxis.	Reserved for patients who have had at least two prior regimens, including lenalidomide and a proteasome inhibitor.
Selinexor, bortezomib, dexamethasone	Thrombocytopenia, neutropenia, and hyponatremia. Neurologic toxicity (eg, dizziness, confusion).	Antiviral prophylaxis; antiemetic prophylaxis.	Reserved for patients with disease refractory to a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.	Must monitor sodium.
Selinexor plus dexamethasone	Thrombocytopenia, neutropenia, and hyponatremia. Neurologic toxicity (eg, peripheral neuropathy, dizziness, confusion).	Antiemetic prophylaxis.	Reserved for patients who have had at least four prior regimens, including at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.	Oral regimen. Must monitor sodium.

This table provides information about select treatment regimens for relapsed or refractory multiple myeloma. The clinician is expected to use his or her independent medical judgment in the context of individual circumstances to make adjustments, as necessary. An autologous hematopoietic cell transplantation should be considered for eligible patients who have not had a transplant before. A second autologous hematopoietic cell transplantation may be considered for patients who progress more than 18 months after transplant without maintenance or more than 36 months after transplantation with maintenance therapy. The immunomodulatory derivatives lenalidomide, pomalidomide, and thalidomide are known teratogens.

PCP: Pneumocystis pneumonia.

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