An open-label phase 2 study treating patients with first or second relapse of multiple myeloma with carfilzomib, pomalidomide, and dexamethasone (KPd): SELECT study

Figures & data

Table 1. Baseline demographics.

Characteristic	KPd 20/56 mg/m^2 N = 52
Median (range) age, years	68 (35–87)
18–<65, n (%)	23 (44)
65–<75, n (%)	21 (40)
75–<85, n (%)	7 (13)
≥85, n (%)	1 (2)
Sex, n (%)
Male	24 (46)
Female	28 (54)
Ethnicity, n (%)
Non-Hispanic/Latino	45 (87)
Hispanic/Latino	4 (8)
Unknown	3 (6)
Race, n (%)
White	47 (90)
Other	5 (10)
ECOG performance status, n (%)
0	27 (52)
1	24 (46)
2	1 (2)
Creatinine clearance (mL/min), n (%)
<30	0
30–<50	7 (13)
50–<80	20 (38)
≥80	25 (48)
R-ISS stage at baseline, n (%)
I	0
II	45 (87)
III	7 (13)
Beta-2 microglobulin level (mg/L), n (%)
<3.5	26 (50)
3.5–<5.5	16 (31)
≥5.5	10 (19)
Cytogenetic risk status,* n (%)
High risk	20 (38)
Standard risk	19 (37)
Missing	13 (25)
Number of prior lines of therapy, n (%)
1	9 (17)
2	43 (83)
Prior transplant, n (%)
Yes	30 (58)
Autologous	29 (56)
Allogeneic	1 (2)
No	22 (42)
Number of prior transplants, n (%)
1	25 (48)
2	5 (10)
Prior bortezomib exposure, n (%)	45 (87)
Refractory to prior bortezomib^†	18 (35)
Prior carfilzomib exposure, n (%)	2 (4)
Refractory to prior carfilzomib^†	1 (2)^ǁ
Prior daratumumab exposure, n (%)	40 (77)
Refractory to prior daratumumab^†	39 (75)
Prior lenalidomide exposure, n (%)	52 (100)
Refractory to prior lenalidomide^†	52 (100)
Prior lenalidomide and PI exposure,^‡ n (%)	46 (88)
Refractory to prior lenalidomide and PI^†	23 (44)
Prior lenalidomide and daratumumab exposure,^‡ n (%)	40 (77)
Refractory to prior lenalidomide and daratumumab^†	39^§ (75)
Prior lenalidomide, PI,^‡ and daratumumab exposure, n (%)	36 (69)
Refractory to prior lenalidomide, PI, and daratumumab^†	19^§ (37)

ECOG: Eastern Cooperative Oncology Group; KPd: carfilzomib, pomalidomide, and dexamethasone; PD: progressive disease; PI: proteosome inhibitor; R-ISS: Revised Multiple Myeloma International Staging System; SD: stable disease.

*High risk was defined as presence of 17p deletion, t(4;14), t(14;16); standard risk was defined as absence of these abnormalities. Missing patients are those who cannot be identified as high risk or standard risk.

^†Patients were considered refractory to bortezomib, carfilzomib, daratumumab, lenalidomide, or PI if any of the following criteria were met: the best response reached during at least one regimen containing the drug of interest was SD or PD, the reason that the drug of interest was stopped was progression in at least one regimen, or date of relapse/progression was after the study start date and within 60 days after the stop date of the drug of interest in at least one regimen.

^‡Including bortezomib, ixazomib, carfilzomib, and oprozomib.

^§Thirty-nine and 19 are not mutually exclusive; 24 (46%) patients were double refractory (4 [8%] were refractory to lenalidomide + PI, and 20 [38%] were refractory to lenalidomide + daratumumab), and 19 (37%) patients were triple refractory.

^ǁThis patient had an SD response to second-line therapy of carfilzomib, lenalidomide, and dexamethasone; based on inclusion criteria, this was a protocol deviation.

Table 2. Overall response.

	KPd 20/56 mg/m^2 N = 52
Best overall response, n (%)
sCR	0 (0)
CR	3 (6)
VGPR	15 (29)
PR	12 (23)
SD	9 (17)
PD	3 (6)
Not evaluable	10 (19)
Patients who achieved a PR or better, n (%)	30 (58)
ORR, % (90% CI)	57.7 (45.4–69.3)
Median DOR, months (90% CI)	20.3 (9.2–NE)
Median (range) TTR, months	1.0 (1–2)
MRD negativity (10^−5) rate, % (90% CI)
MRD– CR at 12 months	n = 2
	3.8 (0.7–11.6)
MRD– rate at any time	n = 5
	9.6 (3.9–19.2)
MRD– CR rate at any time	n = 3
	5.8 (1.6–14.2)
MRD negativity (10^−4) rate, % (90% CI)	n = 7
	13.5 (6.5–23.8)
MRD negativity (10^−6) rate, % (90% CI)	n = 2
	3.8 (0.7–11.6)

CR: complete response; DOR: duration of response; KPd: carfilzomib, pomalidomide, and dexamethasone; MRD: minimal residual disease; NE: not estimable; ORR: overall response rate; PD: progressive disease; PR: partial response; sCR: stringent complete response; SD: stable disease; TTR: time to response; VGPR: very good partial response.

Figure 1. PFS KM curves as assessed by the IRC. IRC: independent review committee; KM: Kaplan-Meier; KPd: carfilzomib, pomalidomide, and dexamethasone; NE: not estimable; PFS: progression-free survival.

Figure 2. OS KM curves. KM: Kaplan-Meier; KPd: carfilzomib, pomalidomide, and dexamethasone; NE: not estimable; OS: overall survival.

Table 3. TEAEs* of interest by preferred term.

TEAE, n (%)	KPd 20/56 mg/m^2 N = 52
TEAEs of interest	42 (81)
Neutropenia	17 (33)
Dyspnea	8 (15)
Upper respiratory tract infection	6 (12)
Hypertension	5 (10)
COVID-19	5 (10)
Acute kidney injury	4 (8)
Leukopenia	4 (8)
Respiratory failure	3 (6)
Lower respiratory tract infection	3 (6)
Dyspnea exertional	3 (6)
Hypotension	2 (4)
Lymphopenia	2 (4)
Pulmonary hypertension	2 (4)
COVID-19 pneumonia	2 (4)
Nasopharyngitis	2 (4)
Pneumonia	2 (4)
Respiratory tract infection	2 (4)
Vision blurred	2 (4)
Acute sinusitis	1 (2)
Asymptomatic COVID-19	1 (2)
Coronavirus infection	1 (2)
Pharyngitis	1 (2)
Rhinitis	1 (2)
Confusional state	1 (2)
Encephalopathy	1 (2)
Cardiac failure	1 (2)
Cardiac failure chronic	1 (2)
Left ventricular failure	1 (2)
Atrial fibrillation	1 (2)
Cardiac arrest	1 (2)
Tricuspid valve incompetence	1 (2)
Eyelid edema	1 (2)
White blood cell decreased	1 (2)

AE: adverse event; KPd: carfilzomib, pomalidomide, and dexamethasone; MedDRA: Medical Dictionary for Regulatory Activities; TEAE: treatment-emergent adverse event.

*TEAEs were events categorized as AEs starting on or after first dose of any study treatment and up to and including 30 days after the last dose of any study treatment, excluding events reported after end of study date. AEs were coded using MedDRA version 25.1. Patients were counted only once for each event of interest and each preferred term.

Table 4. Serious TEAEs.*

TEAE, n (%)	KPd 20/56 mg/m^2 N = 52
Infection/infection-related events
Infection	2 (4)
COVID-19	2 (4)
COVID-19 pneumonia	2 (4)
Sepsis	2 (4)
Pneumonia	2 (4)
Clostridium difficile infection	1 (2)
Cytomegalovirus infection	1 (2)
Lower respiratory tract infection	1 (2)
Hematologic toxicity
Neutropenia	2 (4)
Leukopenia	1 (2)
Thrombocytopenia	1 (2)
Cardiovascular events
Cardiac arrest	1 (2)
Cardiac failure	1 (2)
Cardiac failure chronic	1 (2)
Left ventricular failure	1 (2)
Other events
Respiratory failure	3 (6)
Acute kidney injury	2 (4)
Cerebrovascular accident	2 (4)
Plasma cell myeloma	2 (4)
Pulmonary embolism	1 (2)
Bone pain	1 (2)
Confusional state	1 (2)
Dyspnea	1 (2)
Femoral neck fracture	1 (2)
Osteitis	1 (2)
Plasma cell leukemia	1 (2)
Pyrexia	1 (2)
Renal disorder	1 (2)

AE: adverse event; KPd: carfilzomib, pomalidomide, and dexamethasone; MedDRA: Medical Dictionary for Regulatory Activities; TEAE: treatment-emergent adverse event.

*TEAEs were events categorized as AEs starting on or after first dose of any study treatment and up to and including 30 days after the last dose of any study treatment, excluding events reported after end of study date. AEs were coded using MedDRA version 25.1. Patients were counted only once for each event of interest and each preferred term.

Data availability statement

Qualified researchers may request data from Amgen clinical studies. Complete details are available at the following: http://www.amgen.com/datasharing.