Friday, March 31, 2023
|
|
Patients with del(1p32) |
Patients without del(1p32) |
P value |
|---|---|---|---|
| Patients, n | 282 | 2269 | |
| Age at diagnosis, mean (SD), y | 63.8 (10.8) | 63.6 (10.7) | .9876 |
| Sex, n (%) | .6655 | ||
| Male | 169 (59.9) | 1323 (58.4) | |
| Female | 113 (40.1) | 943 (41.6) | |
| Missing | 0 | 3 | |
| ISS, n (%) | .0177 | ||
| 1 | 48 (21.7) | 540 (29.2) | |
| 2 | 94 (42.5) | 795 (42.9) | |
| 3 | 79 (35.7) | 517 (27.9) | |
| Patients, n | 221 | 1852 | |
| Missing, n | 61 | 417 | |
| Del(17p), n (%) | <.0001 | ||
| No | 217 (77.5) | 2064 (91.2) | |
| Yes | 63 (22.5) | 199 (8.8) | |
| Missing | 2 | 6 | |
| t(4;14), n (%) | .8478 | ||
| No | 245 (88.4) | 1966 (87.8) | |
| Yes | 32 (11.6) | 272 (12.2) | |
| Missing | 5 | 31 | |
| Gain(1q), n (%) | <.0001 | ||
| No | 127 (45.0) | 1502 (66.2) | |
| Yes | 155 (55.0) | 766 (33.8) | |
| Missing | 0 | 1 | |
| t(14;16), n (%) | .0016 | ||
| No | 91 (87.5) | 689 (95.6) | |
| Yes | 13 (12.5) | 32 (4.4) | |
| Missing | 178 | 1,548 | |
| t(14;20), n (%) | .6969 | ||
| No | 67 (98.5) | 301 (96.8) | |
| Yes | 1 (1.5) | 10 (3.2) | |
| Missing | 214 | 1,958 | |
| TP53 mutation, n (%) | .0010 | ||
| No | 55 (72.4) | 288 (88.1) | |
| Yes | 21 (27.6) | 39 (11.9) | |
| Missing | 206 | 1,942 | |
| Hyperdiploidy (>50 chromosomes), n (%) | .0065 | ||
| No | 188 (69.9) | 1336 (61.1) | |
| Yes | 81 (30.1) | 849 (38.9) | |
| Missing | 13 | 84 | |
| First-line therapy, n (%) | |||
| Patients eligible for transplant | |||
| IMiD or PI without anti-CD38 | 20 (14.9) | 178 (15.8) | .1061 |
| Triplet * | 104 (77.6) | 905 (80.6) | |
| Triplet + anti-CD38 | 10 (7.5) | 41 (3.6) | |
| Patients not eligible for transplant | |||
| IMiD or PI without anti-CD38 | 84 (59.2) | 716 (64.0) | .0819 |
| IMiD or PI with anti-CD38 | 11 (7.7) | 41 (3.7) | |
| Triplet | 44 (31.0) | 350 (31.3) | |
| Triplet + anti-CD38 | 3 (2.1) | 12 (1.0) | |
| Missing | 6 | 26 | |
| Maintenance therapy for patients eligible for transplant, n (%) | .3161 | ||
| No | 77 (57.5) | 696 (61.9) | |
| Yes | 57 (42.5) | 428 (38.1) | |
| Missing | 0 | 0 |
Table 1. Characteristics of patients according to deletion-1p32 status
IMiDs, immunomodulatory drugs; ISS, International Staging System; PI, proteasome inhibitors; SD, standard deviation.
*Triplet is defined by the association of 1 IMiD, 1 PI, and 1 corticosteroid (mostly dexamethasone).
|
Variable |
Univariate analysis |
Multivariate analysis |
||||||
|---|---|---|---|---|---|---|---|---|
|
PFS (n = 1860) |
OS (n = 1721 ) |
PFS (n = 1860) |
OS (n = 1721) |
|||||
|
HR (95% CI) |
P value |
HR (95% CI) |
P value |
HR (95% CI) |
P value |
HR (95% CI) |
P value |
|
| Age | 1.0 (1.0-1.0) | <.0001 | 1.0 (1.0-1.0) | <.0001 | ||||
| High-dose melphalan | 1.7 (1.6-1.9) | <.0001 | 1.6 (1.4-1.) | <.0001 | ||||
| ISS II vs I | 1.4 (1.3-1.6) | <.0001 | 1.9 (1.5-2.4) | <.0001 | 1.2 (1.1-1.4) | .0016 | 1.5 (1.2-1.8) | .001 |
| ISS III vs I | 2.0 (1.7-2.3) | <.0001 | 2.9 (2.3-3.6) | <.0001 | 1.7 (1.5-2.0) | <.0001 | 2.1 (1.6-2.6) | <.0001 |
| del(1p32) | 1.5 (1.2-1.7) | <.0001 | 2.5 (2.0-3.1) | <.0001 | 1.3 (1.1-1.5) | .0065 | 1.9 (1.5-2.40) | <.0001 |
| del(17p) | 1.9 (1.6-2.2) | <.0001 | 3.2 (2.6-3.9) | <.0001 | 1.8 (1.5-2.1) | <.0001 | 2.9 (2.3-3.8) | <.0001 |
| t(4;14) | 1.6 (1.4-1.8) | <.0001 | 2.2 (1.8-2.7) | <.0001 | 1.4 (1.2-1.7) | <.0001 | 1.7 (1.4-2.2) | <.0001 |
| Gain(1q) | 1.5 (1.3-1.6) | <.0001 | 1.9 (1.7-2.3) | <.0001 | 1.3 (1.2-1.5) | <.0001 | 1.6 (1.3-1.9) | <.0001 |
Table 2. Univariate and multivariate analyses for PFS and OS
CI, confidence interval; HR, hazard ratio; OS, overall survival; PFS, progression-free survival.
Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™
ABIM Diplomates - maximum of 1.00 ABIM MOC points
This activity is intended for hematologists, oncologists, internists, geneticists, and other physicians caring for patients with newly diagnosed multiple myeloma (NDMM).
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Cytogenetic abnormalities (CAs) are known to be the preponderant prognostic factor in multiple myeloma. Our team has recently developed a prognostic score based on 6 CAs, with which del(1p32) appears to be the second worst abnormality after del(17p). This study aimed to confirm the adverse effect of 1p32 deletion in patients with newly diagnosed multiple myeloma (NDMM). Among 2551 patients with newly diagnosed multiple myeloma, 11% were harboring del(1p32). Their overall survival (OS) was significantly inferior compared with patients without del(1p32) (median OS: 49 months vs 124 months). Likewise, progression-free survival was significantly shorter. More importantly, biallelic del(1p32) conferred a dramatically poorer prognosis than a monoallelic del(1p32) (median OS: 25 months vs 60 months). As expected, the OS of patients with del(1p32) significantly decreased when this abnormality was associated with other high-risk CAs [del(17p), t(4;14), or gain(1q)]. In the multivariate analysis, del(1p32) appeared as a negative prognostic factor; after adjustment for age and treatment, the risk of progression was 1.3 times higher among patients harboring del(1p32), and the risk of death was 1.9 times higher. At the dawn of risk-adapted treatment strategies, we have confirmed the adverse effect of del(1p32) in multiple myeloma and the relevance of its assessment at diagnosis.
Multiple myeloma (MM) is the second most frequent hematological malignancy in Western countries. The exceptional development in patient treatments has led to a significant improvement in overall survival (OS), both for patients who are eligible for transplant and for those who are not.[1] However, this improvement does not benefit patients at high risk who still represent an unmet medical need. It is unanimously recognized that cytogenetic abnormalities (CAs) displayed by malignant plasma cells (PCs) have a strong prognostic impact. Deletion 17p [del(17p)] is known to be the most unfavorable CA and affects ~8% of patients with newly diagnosed MM (NDMM). In 2015, del(17p) was integrated into the criteria of the revised version of the International Staging System (ISS) score, as well as 2 other CAs, translocations t(4;14) and t(14;16).[2]
CAs affecting chromosome 1, gain(1q) and del(1p32), were not included in these new criteria despite their relatively high frequencies, 35% and 11%, respectively, in patients with NDMM. However, previous or subsequent studies have distinctly demonstrated their negative effect on patients.[3-5] Moreover, Perrot et al have recently confirmed the significant prognostic impact of del(1p32) as being the second most adverse abnormality in myeloma, just after del(17p).[6]
This study aimed to update our data on the prognostic impact of del(1p32) in a large cohort of patients with NDMM, irrespectively of the therapeutic strategy used.
