Table 1.
Baseline clinical and treatment characteristics by regimens for LOT ≥ 2
| Variable (%) | Rd backbone cohort, N = 820 | Pd backbone cohort, N = 392 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| VRd (N = 349) | KRd (N = 218) | DRd (N = 99) | IRd (N = 154) | P-value | VPd (N = 52) | KPd (N = 146) | DPd (N = 149) | IPd (N = 45) | P-value | |
| Age, median years (IQR)a | 70 (62, 78) | 64 (56, 74) | 70 (61, 75) | 70 (62, 79) | < 0.01 | 70 (64, 75) | 66 (60, 73) | 68 (60, 74) | 67 (63, 77) | 0.07 |
| Age group, years | ||||||||||
| 18–64 | 34.1 | 50.9 | 37.4 | 36.4 | < 0.01 | 26.9 | 43.2 | 36.9 | 35.6 | 0.10 |
| 65–74 | 29.2 | 27.5 | 36.4 | 24.0 | 44.2 | 37.7 | 39.6 | 26.7 | ||
| ≥ 75 | 36.7 | 21.6 | 26.3 | 39.6 | 28.9 | 19.2 | 23.5 | 37.8 | ||
| CCI scoreb,c | ||||||||||
| 0 | 28.9 | 27.0 | 27.3 | 39.0 | 0.06 | 32.7 | 23.3 | 23.5 | 42.2 | 0.10 |
| 1 | 10.0 | 9.2 | 15.2 | 11.0 | 7.7 | 16.4 | 9.4 | 11.1 | ||
| ≥ 2 | 61.0 | 63.8 | 57.6 | 50.0 | 59.6 | 60.3 | 67.1 | 46.7 | ||
| ECOG PS | ||||||||||
| 0–1 | 15.5 | 18.4 | 21.2 | 15.6 | 0.30 | 42.3 | 18.5 | 22.1 | 13.3 | 0.02 |
| 2–4 | 2.0 | 3.2 | 5.1 | 2.0 | 0.0 | 4.1 | 4.0 | 2.2 | ||
| Unknown | 82.5 | 78.4 | 73.7 | 82.5 | 57.7 | 77.4 | 73.8 | 84.4 | ||
| Cytogeneticsd | ||||||||||
| High risk | 11.8 | 25.7 | 10.1 | 14.9 | < 0.01 | 17.3 | 26.0 | 33.6 | 11.1 | < 0.01 |
| Not high risk/unk | 88.3 | 74.3 | 89.9 | 85.1 | 82.7 | 74.0 | 66.4 | 88.9 | ||
| CRAB symptomsb,e | ||||||||||
| Any | 78.5 | 84.4 | 78.8 | 63.6 | < 0.01 | 76.9 | 86.3 | 86.6 | 62.2 | 0.01 |
| Hypercalcemia | 10.6 | 12.8 | 10.1 | 6.5 | 0.22 | 9.6 | 14.4 | 15.4 | 4.4 | 0.06 |
| RI | 47.9 | 42.7 | 52.5 | 29.2 | < 0.01 | 42.3 | 44.5 | 53.0 | 20.0 | < 0.01 |
| Anemia | 65.6 | 75.2 | 64.7 | 56.5 | < 0.01 | 69.2 | 80.1 | 82.6 | 46.7 | < 0.01 |
| Bone disease | 19.8 | 25.7 | 26.3 | 18.2 | 0.18 | 26.9 | 27.4 | 29.5 | 17.8 | 0.40 |
| Baseline PN | 11.5 | 22.5 | 31.3 | 19.5 | < 0.01 | 9.6 | 24.0 | 22.2 | 31.5 | < 0.01 |
| Baseline CVD | 28.6 | 26.6 | 25.3 | 19.5 | 0.14 | 26.9 | 23.3 | 31.5 | 13.3 | 0.05 |
| ISS stage | ||||||||||
| I/II | 20.1 | 20.6 | 16.2 | 11.0 | 0.64 | 15.4 | 27.4 | 18.8 | 15.6 | NE |
| III | 5.4 | 6.0 | 2.0 | 2.6 | 7.7 | 6.2 | 6.0 | 0.0 | ||
| Unk | 74.5 | 73.4 | 81.8 | 86.4 | 76.9 | 66.4 | 75.2 | 84.4 | ||
| Site of care | ||||||||||
| Community | 45.0 | 39.5 | 37.4 | 44.8 | 0.11 | 32.7 | 28.1 | 36.9 | 37.8 | 0.09 |
| Academic | 21.2 | 18.4 | 16.2 | 18.2 | 25.0 | 31.5 | 16.8 | 28.9 | ||
| Unknown | 33.8 | 42.2 | 46.5 | 37.0 | 42.3 | 40.4 | 46.3 | 33.3 | ||
| Year of diagnosis | ||||||||||
| 2007–2011 | 18.1 | 18.8 | 13.1 | 20.1 | 0.48 | 42.3 | 32.2 | 24.2 | 33.3 | 0.06 |
| 2012–2015 | 63.3 | 63.3 | 64.6 | 61.7 | 51.9 | 60.3 | 65.8 | 60.0 | ||
| 2016–2017 | 18.6 | 17.9 | 22.2 | 18.2 | 5.8 | 7.5 | 10.1 | 6.7 | ||
| Index LOT | ||||||||||
| 2 | 69.3 | 46.3 | 30.3 | 40.9 | < 0.01 | 28.6 | 20.6 | 11.4 | 17.8 | < 0.01 |
| 3 | 19.8 | 25.2 | 25.3 | 29.2 | 25.0 | 24.0 | 16.1 | 26.7 | ||
| 4 | 7.5 | 16.1 | 18.2 | 16.9 | 26.9 | 24.7 | 28.2 | 15.6 | ||
| ≥ 5 | 3.4 | 12.4 | 26.3 | 13.0 | 19.2 | 30.8 | 44.3 | 40.0 | ||
| Prior exposure to IMIDs or PIs | ||||||||||
| IMID and PI | 31.5 | 67.0 | 67.7 | 57.8 | < 0.01 | 71.2 | 89.7 | 86.6 | 75.6 | 0.02 |
| PI only | 42.1 | 26.2 | 21.2 | 13.0 | < 0.01 | 86.5 | 93.2 | 96.0 | 97.8 | 0.13 |
| IMID only | 23.5 | 5.5 | 10.1 | 27.9 | < 0.01 | 11.5 | 2.7 | 8.7 | 22.2 | < 0.01 |
| Prior dara | 0.0 | 4.6 | 24.2 | 5.8 | NE | 1.9 | 9.6 | 28.9 | 2.2 | < 0.01 |
| Refractory status to PIs and/or IMIDs | ||||||||||
| Both IMID and PI | 3.4 | 21.6 | 31.3 | 22.1 | < 0.01 | 25.0 | 59.6 | 68.5 | 44.4 | 0.29 |
| IMID only | 8.0 | 6.4 | 3.0 | 9.7 | 38.5 | 15.1 | 11.4 | 28.9 | ||
| PI only | 3.4 | 53.2 | 39.4 | 25.3 | 7.7 | 10.3 | 14.8 | 13.3 | ||
| Neither | 85.1 | 18.8 | 26.3 | 42.9 | 28.9 | 15.1 | 5.4 | 13.3 | ||
| Refractory to prior LOTf | 80.0 | 85.3 | 81.8 | 70.8 | 0.01 | 78.9 | 84.9 | 87.3 | 86.7 | 0.60 |
| Prior SCT | 15.8 | 33.5 | 41.4 | 16.9 | < 0.01 | 32.7 | 31.5 | 38.9 | 28.9 | 0.67 |
| Time from diagnosis to index LOT | ||||||||||
| Median (IQR) | 17.9 (8.3, 35.9) | 21.0 (10.6, 42.1) | 35.7 (18.8, 52.3) | 32.7 (16.5, 55.2) | < 0.01 | 32.9 (24.5, 59.5) | 32.1 (15.9, 55.2) | 38.0 (24.8, 60.6) | 52.8 (31.6, 67.2) | 0.02 |
| Time from start of LOT1 to start of LOT2 | ||||||||||
| Median (IQR) | 10.1 (5.3, 17.9) | 9.9 (5.3, 16.6) | 12.6 (6.9, 25.5) | 15.0 (9.3, 24.0) | < 0.01 | 14.0 (7.7, 25.5) | 11.3 (6.5, 20.7) | 12.6 (7.1, 23.3) | 17.3 (7.9, 24.7) | 0.21 |
aAge at the time of initiation of LOT ≥ 2
bBaseline presence is relative to 6 months prior to initiation of index LOT with the value closest to index LOT initiation, recorded
cSource: Quan 2002 [22]
dHigh-risk cytogenetics were defined as presence of del[17p], t[4;14], t[14;16], and/or 1q21 gain
eCRAB definitions: hypercalcemia (identified via ICD-9/10 code or lab value indicating corrected serum calcium > 11 mg/dL), renal insufficiency (defined as lab value indicating serum creatinine > 2 mg/dL or creatinine clearance < 40 mL/min), anemia (identified via ICD-9/10 code or hemoglobin level < 10 gm/dL), and bone lesions (proxied by fracture, radiation, bone-directed surgery, or spinal cord compression) (Nash 2016) [23]
fRefractory status to prior LOT was defined as a TFI of < 60 days between previous LOT and index LOT
Key: CCI, Charlson comorbidity index; Dara, daratumumab; DPd, daratumumab, pomalidomide, dexamethasone; DRd, daratumumab, lenalidomide, dexamethasone; IMID, immunomodulatory drug; IPd, ixazomib, pomalidomide, dexamethasone; IQR, interquartile range; IRd, ixazomib, lenalidomide, dexamethasone; ISS, International Staging System; KPd, carfilzomib, pomalidomide, dexamethasone; KRd, carfilzomib, lenalidomide, dexamethasone; LOT, line of therapy; PI, proteasome inhibitor; RI, renal insufficiency; SCT, stem cell transplant; sxs, symptoms; TFI, treatment-free interval; Unk, unknown; VPd, bortezomib, pomalidomide, dexamethasone; VRd, bortezomib, lenalidomide, dexamethasone