Real-world outcomes for multiple myeloma patients after apheresis for planned chimeric antigen receptor T-cell therapy

Table 1 Baseline characteristics of patients with relapsed or refractory multiple myeloma who underwent apheresis for planned chimeric antigen receptor T-cell infusion, n (%)

Characteristic	CAR-T infused (n = 87)	Not infused (n = 12)	P value	Test
Age at apheresis, year, median (range)	67.7 (36.7-81.7)	70.2 (42.6-83.7)	0.415	Wilcoxon
Sex	Not evaluable (missing 87/87)	Not evaluable (missing 12/12)	-	-
Plasma cell leukaemia	3/87 (3.4)	3/12 (25.0)	0.017	Fisher
Extramedullary disease	17/87 (19.5)	9/12 (75.0)	< 0.001	Fisher
High-risk cytogenetics1	29/85 (34.1)	4/11 (36.4)	0.88	Fisher
Missing	2	1	-	-
R-ISS stage	-	-	0.19	Fisher
I	11/66 (16.7)	1/11 (9.1)	-	-
II	52/66 (78.8)	8/11 (72.7)	-	-
III	3/66 (4.5)	2/11 (18.2)	-	-
Not evaluable	21	1	-	-
Prior lines of therapy, median (range)	5 (2-19)	5 (4-8)	0.431	Wilcoxon
Prior autologous or allogeneic transplant	81/87 (93.1)	10/12 (83.3)	0.24	Fisher
Bridging therapy after apheresis	33/87 (37.9)	5/12 (41.7)	0.80	Fisher
Apheresis-to-infusion interval, days, median (IQR; range)	54 (46-62; 37-202), n = 842	Not applicable	-	-
Lymphodepleting regimen
Fludarabine/cyclophosphamide	43/87 (49.4)	-	-	-
Bendamustine	44/87 (50.6)	-	-	-
Intended/administered CAR-T product	-	-	0.55	Fisher
Ciltacabtagene autoleucel	45/87 (51.7)	6/12 (50.0)	-	-
Idecabtagene vicleucel	42/87 (48.3)	6/12 (50.0)	-	-

¹High-risk cytogenetics.

²Apheresis-to-infusion interval data were not evaluable/missing for 3 of the 87 infused patients.

CAR-T: Chimeric antigen receptor T-cell; R-ISS: Revised International Staging System; IQR: Interquartile range.

Table 2 Patient-level characteristics and outcomes of the 12 patients who underwent apheresis but were not infused

ID	Age band (year)	EMD	PCL	High-risk cyto	R-ISS	Prior lines	Intended product	Bridging regimen (category)	Days apheresis → attrition event	Reason not infused	Subsequent therapy	Outcome (months from apheresis)
N-01	60-64	Yes	No	No	II	7	Ide-cel	None	176	Infection (bacteraemia, prolonged admission)	None	Died, 5.8
N-02	80-84	No	No	No	II	4	Ide-cel	None	11	Non-myeloma death (COVID-19, pulmonary embolism)	None	Died, 1.0
N-03	75-79	Yes	No	No	I	6	Ide-cel	Antibody-drug conjugate	70	Non-myeloma death (ischaemic stroke)	None	Died, 2.3
N-04	60-64	Yes	Yes	Yes	II	4	Cilta-cel	PI + BCL2 inhibitor + steroid	34	Manufacturing failure (out-of-specification product)	BCMA bispecific	Died, 6.2
N-05	55-59	Yes	No	No	II	5	Cilta-cel	None	24	Progressive disease + intracranial haemorrhage	None	Died, 0.8
N-06	75-79	Yes	No	Yes	II	4	Ide-cel	Radiotherapy	71	Progressive disease → bowel ischaemia	None	Died, 2.3
N-07	40-44	No	Yes	Yes	III	5	Cilta-cel	None	51	Progressive disease; declined further therapy	None	Lost to follow-up; censored 1.7
N-08	80-84	Yes	No	No	II	5	Cilta-cel	Alkylator + PI + steroid	47	Progressive disease	None	Died, 1.5
N-09	65-69	Yes	No	Yes	II	5	Ide-cel	BCMA bispecific	33	Progressive disease	None	Died, 1.1
N-10	60-64	Yes	Yes	No	III	8	Cilta-cel	None	5	Progressive disease	None	Died, 0.2
N-11	80-84	Yes	No	Unknown	Unknown	7	Ide-cel	None	196	Collection failure (inadequate CD3+ yield)	GPRC5D bispecific	Alive, 11.7
N-12	70-74	No	No	No	II	5	Cilta-cel	None	42	Progressive disease	None	Died, 1.4

Median time from apheresis to the attrition event: 44 days (interquartile range: 30-72; range 5-196). Eight of 12 events (66.7%) occurred within 60 days. Ages are banded and no dates are reported, to protect confidentiality. BCMA: B-cell maturation antigen; EMD: Extramedullary disease; GPRC5D: G protein-coupled receptor class C group 5 member D; PCL: Plasma cell leukaemia; PI: Proteasome inhibitor; R-ISS: Revised International Staging System; COVID-19: Coronavirus disease 2019; BCL2: B-cell lymphoma 2.

Table 3 Univariable logistic regression: Baseline correlates of failure to reach chimeric antigen receptor T-cell infusion (n = 99; 12 events), n (%)

Variable	Not infused	Infused	OR (95%CI)	P value
Extramedullary disease	9/12 (75.0)	17/87 (19.5)	12.4 (3.0-50.6)	< 0.001
Plasma cell leukaemia	3/12 (25.0)	3/87 (3.4)	9.3 (1.6-53.4)	0.012
R-ISS stage III (vs I-II)	2/11 (18.2)	3/66 (4.5)	4.7 (0.7-31.9)	0.13
High-risk cytogenetics	4/11 (36.4)	29/85 (34.1)	1.10 (0.30-4.05)	0.88
Age (per 10 years)	Median 70.2	Median 67.7	1.24 (0.71-2.16)	0.45
Prior lines of therapy	Median 5	Median 5	-	0.4311

¹Wilcoxon rank-sum test; not modelled. Estimates are univariable, unadjusted for multiplicity, and unstable given 12 events. No multivariable model was fitted (events per variable < 10).

CI: Confidence interval; OR: Odds ratio; R-ISS: Revised International Staging System.

Table 4 Kaplan-Meier estimates and numbers at risk from the date of apheresis

Months from apheresis	0	3	6	12	18	24	30
PFS - infused: At risk	87	82	65	37	16	6	1
PFS - infused: % (95%CI)	100	94.3 (86.7-97.6)	81.0 (71.2-87.6)	67.9 (56.9-76.8)	49.2 (37.5-60.0)	32.6 (21.1-44.6)	20.9 (9.6-35.2)
PFS - not infused: At risk	12	2	1	0	0	0	0
PFS - not infused: % (95%CI)	100	16.7 (2.7-41.3)	8.3 (0.5-31.1)	0	0	0	0
OS - infused: At risk	87	85	76	50	27	15	6
OS - infused: % (95%CI)	100	97.7 (91.1-99.4)	94.1 (86.6-97.4)	88.6 (79.6-93.8)	82.7 (72.2-89.5)	75.1 (62.6-84.0)	65.7 (48.3-78.5)
OS - not infused: At risk	12	3	2	0	0	0	0
OS - not infused: % (95%CI)	100	25.0 (6.0-50.5)	20.0 (3.5-46.0)	10.0 (0.6-35.8)	0	0	0

Median progression-free survival: Infused 17.5 months [95% confidence interval (CI): 12.7-21.6); not infused 1.5 months (95%CI 0.8-2.3)]; log-rank P < 0.001. Median overall survival: Infused not reached (95%CI not estimable); not infused 1.9 months (95%CI 1.0-6.2); log-rank P < 0.001. Where the survival function equalled exactly 0.50 across an interval, the median is reported as the interval midpoint. CI: Confidence interval; OS: Overall survival; PFS: Progression-free survival.