Characteristics of different subgroups of patients with PMBL from the 5ʹRACE cohort: patients with PMBL with HCD (n = 12) vs others (n = 63)
| Characteristics . | HCD, n = 12 (16%) . | Others, n = 63 (84%) . | P value . | Adjusted P value . |
|---|---|---|---|---|
| Age, median (Q1; Q3, min-max), y | 40 (25.5; 49.25, 18-57) | 32 (26; 40, 19-64) | .308 | .583 |
| Female sex | 7 (58.33%) | 33 (52.38%) | .762 | .903 |
| ECOG 0-1 | 11 (91.67%) | 54 (85.71%) | 1 | 1 |
| Ann Arbor stage I-II | 6 (50%) | 37 (58.73%) | .752 | .903 |
| Elevated LDH | 10 (83.33%) | 51 (80.95%) | 1 | 1 |
| IPI 0 | 0 (0%) | 9 (14.29%) | .566 | .823 |
| IPI 1-2 | 9 (75%) | 39 (61.9%) | ||
| IPI 3-5 | 3 (25%) | 15 (23.81%) | ||
| Bulky mass ≥10 cm | 8 (66.67%) | 37 (58.73%) | .752 | 0.903 |
| Extranodal involvement | 8 (66.67%) | 35 (55.56%) | .54 | .823 |
| First-line treatment | ||||
| Anti CD20 + ACVBP | 10 (83.33%) | 44 (69.84%) | .888 | .982 |
| Anti CD20 + CHOP14 | 1 (8.33%) | 10 (15.87%) | ||
| Anti CD20 + CHOP21 | 1 (8.33%) | 9 (14.29%) | ||
| Baseline median MTV (Q1; Q3, min-max), cm3 | 369.71 (265.44; 582.42, 166.82-1147.52) | 249.17 (138.09; 405.52, 20.22-1066.3) | .094 | 0.273 |
| MTV ≥360 cm3 | 5 (50%) | 16 (32%) | .298 | .583 |
| GEP assay (RT-MLPA) | ||||
| High CD20 gene expression (greater than median∗) | 8 (66.67%) | 29 (46.03%) | .222 | .547 |
| High MAL expression (> greater than median∗) | 9 (75%) | 28 (44.44%) | .065 | .207 |
| Low CD3 expression (less than or equal to median∗) | 8 (66.67%) | 30 (47.62%) | .346 | .583 |
| Low CD68 expression (less than or equal to median∗) | 8 (66.67%) | 30 (47.62%) | .346 | .583 |
| High AID expression (greater than median∗) | 9 (75%) | 28 (44.44%) | .065 | .207 |
| High PDL1/PDL2 expression (PDL1 > 0.402; PDL2 > 9.147) | 8 (66.67%) | 14 (22.22%) | .004 | .043 |
| 5′RACE assay | ||||
| Presence of a fusion transcript involving IgVH or IgVL | 2 (16.67%) | 4 (6.35%) | .244 | .557 |
| Confirmed IgVH clonality | 12 (100%) | 48 (76.19%) | .109 | .291 |
| Isotype heavy chain | ||||
| IgM | 2 (16.67%) | 3 (6.25%) | .602 | .837 |
| IgD | 0 (0%) | 1 (2.08%) | ||
| IgG | 7 (58.33%) | 33 (68.75%) | ||
| IgE | 0 (0%) | 3 (6.25%) | ||
| IgA | 3 (25%) | 8 (16.67%) | ||
| Confirmed IgVL clonality | 12 (100%) | 47 (74.6%) | .059 | .207 |
| Isotype light chain | ||||
| Kappa | 8 (66.67%) | 27 (57.45%) | .745 | .903 |
| Lambda | 4 (33.33%) | 20 (42.55%) | ||
| Confirmed IgVH and IgVL clonality | 12 (100%) | 44 (69.84%) | .030 | .163 |
| Homology rate with the germ line sequence | ||||
| IgVH, median (Q1; Q3, min-max) | 85.52 (83.43; 86.52, 71.95-97.7) | 85.42 (78.88; 92.35, 64.21-99.37) | .89 | .982 |
| IgVL, median (Q1; Q3, min-max) | 89.42 (86.56; 92.31, 77.5-99.26) | 86.42 (79.82; 92.28, 73.45-99.13) | .413 | .66 |
| Simpson heterogeneity index for IgVH, median (Q1; Q3, min-max) | 0.66 (0.55; 0.71, 0.34-0.79) | 0.14 (0.02; 0.32, 0-0.87) | <.001 | <.001 |
| Simpson heterogeneity index for IgVL, median (Q1; Q3, min-max) | 0.59 (0.54; 0.73, 0.43-0.87) | 0.15 (0.01; 0.49, 0-0.74) | <.001 | <.001 |
| Characteristics . | HCD, n = 12 (16%) . | Others, n = 63 (84%) . | P value . | Adjusted P value . |
|---|---|---|---|---|
| Age, median (Q1; Q3, min-max), y | 40 (25.5; 49.25, 18-57) | 32 (26; 40, 19-64) | .308 | .583 |
| Female sex | 7 (58.33%) | 33 (52.38%) | .762 | .903 |
| ECOG 0-1 | 11 (91.67%) | 54 (85.71%) | 1 | 1 |
| Ann Arbor stage I-II | 6 (50%) | 37 (58.73%) | .752 | .903 |
| Elevated LDH | 10 (83.33%) | 51 (80.95%) | 1 | 1 |
| IPI 0 | 0 (0%) | 9 (14.29%) | .566 | .823 |
| IPI 1-2 | 9 (75%) | 39 (61.9%) | ||
| IPI 3-5 | 3 (25%) | 15 (23.81%) | ||
| Bulky mass ≥10 cm | 8 (66.67%) | 37 (58.73%) | .752 | 0.903 |
| Extranodal involvement | 8 (66.67%) | 35 (55.56%) | .54 | .823 |
| First-line treatment | ||||
| Anti CD20 + ACVBP | 10 (83.33%) | 44 (69.84%) | .888 | .982 |
| Anti CD20 + CHOP14 | 1 (8.33%) | 10 (15.87%) | ||
| Anti CD20 + CHOP21 | 1 (8.33%) | 9 (14.29%) | ||
| Baseline median MTV (Q1; Q3, min-max), cm3 | 369.71 (265.44; 582.42, 166.82-1147.52) | 249.17 (138.09; 405.52, 20.22-1066.3) | .094 | 0.273 |
| MTV ≥360 cm3 | 5 (50%) | 16 (32%) | .298 | .583 |
| GEP assay (RT-MLPA) | ||||
| High CD20 gene expression (greater than median∗) | 8 (66.67%) | 29 (46.03%) | .222 | .547 |
| High MAL expression (> greater than median∗) | 9 (75%) | 28 (44.44%) | .065 | .207 |
| Low CD3 expression (less than or equal to median∗) | 8 (66.67%) | 30 (47.62%) | .346 | .583 |
| Low CD68 expression (less than or equal to median∗) | 8 (66.67%) | 30 (47.62%) | .346 | .583 |
| High AID expression (greater than median∗) | 9 (75%) | 28 (44.44%) | .065 | .207 |
| High PDL1/PDL2 expression (PDL1 > 0.402; PDL2 > 9.147) | 8 (66.67%) | 14 (22.22%) | .004 | .043 |
| 5′RACE assay | ||||
| Presence of a fusion transcript involving IgVH or IgVL | 2 (16.67%) | 4 (6.35%) | .244 | .557 |
| Confirmed IgVH clonality | 12 (100%) | 48 (76.19%) | .109 | .291 |
| Isotype heavy chain | ||||
| IgM | 2 (16.67%) | 3 (6.25%) | .602 | .837 |
| IgD | 0 (0%) | 1 (2.08%) | ||
| IgG | 7 (58.33%) | 33 (68.75%) | ||
| IgE | 0 (0%) | 3 (6.25%) | ||
| IgA | 3 (25%) | 8 (16.67%) | ||
| Confirmed IgVL clonality | 12 (100%) | 47 (74.6%) | .059 | .207 |
| Isotype light chain | ||||
| Kappa | 8 (66.67%) | 27 (57.45%) | .745 | .903 |
| Lambda | 4 (33.33%) | 20 (42.55%) | ||
| Confirmed IgVH and IgVL clonality | 12 (100%) | 44 (69.84%) | .030 | .163 |
| Homology rate with the germ line sequence | ||||
| IgVH, median (Q1; Q3, min-max) | 85.52 (83.43; 86.52, 71.95-97.7) | 85.42 (78.88; 92.35, 64.21-99.37) | .89 | .982 |
| IgVL, median (Q1; Q3, min-max) | 89.42 (86.56; 92.31, 77.5-99.26) | 86.42 (79.82; 92.28, 73.45-99.13) | .413 | .66 |
| Simpson heterogeneity index for IgVH, median (Q1; Q3, min-max) | 0.66 (0.55; 0.71, 0.34-0.79) | 0.14 (0.02; 0.32, 0-0.87) | <.001 | <.001 |
| Simpson heterogeneity index for IgVL, median (Q1; Q3, min-max) | 0.59 (0.54; 0.73, 0.43-0.87) | 0.15 (0.01; 0.49, 0-0.74) | <.001 | <.001 |
HCD cases were defined as those with dominant clonotypes representing >81.1% and >78.6% of all CDR3 sequences for IgVH and IgVL, respectively. Bold values indicate that statistical significance was reached (P < .05).
ECOG, Eastern Cooperative Oncology Group; IPI, International Prognostic Index; LDH, lactate dehydrogenase; min-max, minimum-maximum; Q, quartile; RT-MLPA, reverse transcription multiplex ligation-dependent probe amplification.
Median values of each marker, defined in the overall population included in the 5′RACE set, are described in Table 1.