Table 2.

Patient Populations Targeted in Recent Registration Studies of Novel Agents in Multiple Myeloma and Associated Adverse Events¹

Trial	Agent or Regimen	Target Population	Enrolled Population (% with 1, 2, 3 prior lines)	Key Exclusion Criteria	Adverse Events Increased in Experimental Arm*
PANORAMA1	Panobinostat/Bortezomib/dex	Relapsed or refractory with 1–3 prior therapies	51% / 32% / 17%	Primary refractory or bortezomib-refractory myeloma	Diarrhea, fatigue, nausea, peripheral edema, anorexia, pyrexia, vomiting, thrombo-cytopenia, leukopenia, neutropenia, and anemia
	Placebo/Bortezomib/dex		52% / 28% / 20%
ASPIRE	Carfilzomib/Lenalidomide/dex	Relapsed disease after 1–3 prior lines of therapy	46.5% / 53.3% with 2 or 3 lines	Bortezomib-refractory disease excluded. RD allowed if not most recent tx, and no progression during first three RD months.	Cough and hypokalemia
	Lenalidomide/dex		39.6% / 60.1% with 2 or 3 lines
SIRIUS	Daratumumab	Refractory disease with ≥3 lines including PI & IMiD, or refractory to both.	Median of 5 (range 2–14)	None	Not applicable (non-randomized study)
TOURMALINE 1	Ixazomib/Lenalidomide/dex	Relapsed or refractory with 1–3 prior therapies	62% / 27% / 11%	Patients with disease refractory to lenalidomide or a PI	Thrombocytopenia, rash, and vomiting
	Placebo/Lenalidomide/dex		60% / 31% / 9%
ELOQUENT-2	Elotuzumab/Lenalidomide/dex	Relapsed after 1–3 prior therapies	47% with 1 regimen, 37% with 2, 16% with ≥3	Prior len permitted (in ≤10%) if achieved ≥PR, did not progress on or within 9 months of therapy, did not discontinue due to ≥grade 3 AE, had <9 cycles, had ≥9 months between last dose & PD.	Pyrexia, diarrhea, cough
	Lenalidomide/dex		49% with 1 regimen, 35% with 2, 16% with ≥3
ENDEAVOR	Carfilzomib/dex	Patients with relapsed or refractory myeloma after 1–3 prior lines of therapy.	49.8% / 50.2% with 2 or 3 lines	Bortezomib or carfilzomib allowed if these were tolerated, induced a ≥PR before progression, and if patients had a six-month PI-free period	Anemia, dyspnea, pyrexia, cough, hypertension, and muscle spasms
	Bortezomib/dex		49.2% / 50.8% with 2 or 3 lines
CASTOR	Daratumumab/Bortezomib/dex	Relapsed or refractory myeloma after ≥1 prior line(s) of therapy.	48.6% / 27.9% / 14.7% / 8.8% >3 prior lines	Primary refractory disease. Patients refractory or intolerant to bortezomib, or another proteasome inhibitor.	Thrombocytopenia, cough
	Bortezomib/dex		45.7% / 30.0% / 13.0% / 11.3% >3 prior lines
POLLUX	Daratumumab/Lenalidomide/dex	Relapsed or refractory myeloma after ≥1 prior line of therapy	Median of 1 (range 1–11)	Lenalidomide-refractory or intolerant disease	Neutropenia, diarrhea, upper respiratory infection, cough
	Lenalidomide/dex		Median of 1 (range 1–8)

¹Abbreviations: AE, adverse event; dex, dexamethasone, IMiD, immunomodulatory drug; len, lenalidomide; PD, disease progression; PI, proteasome inhibitor; PR, partial remission; RD, lenalidomide a›nd dexamethasone; tx, therapy

^*Adverse events of all grades are listed whose overall incidence was increased in the experimental arm by at least an absolute value of 10% compared with the control arm, where applicable