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Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study

Michael Crump, Sattva S. Neelapu, Umar Farooq, Eric Van Den Neste, John Kuruvilla, Jason Westin, Brian K. Link, Annette Hay, James R. Cerhan, Liting Zhu, Sami Boussetta, Lei Feng, Matthew J. Maurer, Lynn Navale, Jeff Wiezorek, William Y. Go and Christian Gisselbrecht

Data supplements

Article Figures & Data

Figures

  • Figure 1.

    Patient inclusion and search criteria in SCHOLAR-1. Diagram of (A) patients with refractory DLBCL included in the SCHOLAR-1 analysis and (B) search criteria for refractory DLBCL included in SCHOLAR-1. CCTG, Canadian Cancer Trials Group; PD, progressive disease; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; SD, stable disease.

  • Figure 2.

    Response rates by subgroup. The vertical line within the plot represents the objective response rate of 26%. CI, confidence interval; N, the total number of patients in the patient subgroup; n, the number of patients with response.

  • Figure 3.

    Overall survival from commencement of salvage therapy. Shown for the (A) overall population, (B) refractory subgroups, (C) tumor response, and (D) post-refractory transplantation status (Kaplan-Meier).

Tables

  • Table 1.

    Baseline patient characteristics

    CharacteristicMDACC (n = 165)IA/MC (n = 82)LY.12 (CCTG) (n = 219)CORAL (LYSARC) (n = 170)Pooled (N = 636)
    Median age, y (range)56 (20-81)60 (20-80)54 (24-70)54 (19-65)55 (19-81)
    Male sex, %6462616964
    Primary diagnosis, %
     DLBCL*76898410087
     PMBCL10502
     TFL301004
     Indeterminate/missing08001
    ECOG PS, %
     0-14272898473
     2-41024111514
     Missing4940113
    Disease stage, %
     I-II1820333227
     III-IV8279676772
     Missing0101<1
    IPI risk classification, %
     Low risk522363225
     Low-intermediate risk731302924
     High-intermediate to high risk2348353433
     Missing or incompletely assessed6500518
    Refractory category, %
     Primary refractory024512828
     Refractory to ≥ second-line therapy9051214650
     Relapsed ≤12 mo post-ASCT1024282622
    Total no. of lines of chemotherapy and ASCT received, %
     1024512828
     29050214649
     30100<1
     ≥45
    • CCTG, Canadian Cancer Trials Group; LYSARC, Lymphoma Academic Research Organization.

    • * In the CORAL (LYSARC) study, the disease subtype for 96 patients was not available; per the study inclusion criteria, patients were to have DLBCL.

    • IPI was determined at diagnosis for MDACC and IA/MC and at randomization for LY.12 and CORAL study patients; low risk, 0-1 point; low-intermediate risk, 2 points; high-intermediate to high risk, ≥3 points.

  • Table 2.

    Rate of response to chemotherapy after refractory disease

    MDACC (n = 165)IA/MC (n = 82)LY.12 (CCTG) (n = 219)CORAL (LYSARC) (n = 170)Pooled* (N = 636)
    Patients evaluated for response, n16582106170523
    Response rate, % (95% CI)2026263126 (21-31)
     CR rate772157 (3-15)
     PR rate1318251618 (13-23)
    Response rate by refractory category, % (95% CI)
     Primary refractory
      RR25271020 (11-34)
      CR rate10123 (1-11)
     Refractory to second-line or later-line therapy
      RR2021204026 (17-39)
      CR rate75201810 (5-20)
     Relapse ≤12 mo post-ASCT
      RR19353934 (24-45)
      CR rate6102515 (6-31)
    • Response rate to the line of therapy was given after determination of refractory status.

    • CI, confidence interval; RR, response rate.

    • * Higgin’s Q statistic, P = .18.

    • Data contain evidence that the patient proceeded to salvage therapy, but response information was not collected.

  • Table 3.

    Overall survival by relapsed/refractory status

    MDACC (n = 165)IA/MC (n = 82)LY.12 (CCTG) (n = 219)CORAL (LYSARC) (n = 170)Pooled (N = 636)
    Patients evaluated for survival, n16572196170603
    Survival from start of salvage therapy
     Deaths8992808084
     Median, mo (95% CI)6.65.06.66.56.3 (5.9-7.0)
     1-y survival rate2818313028 (25-32)
     2-y survival rate1710232220 (16-23)
    Primary refractory
     Deaths90768580
     Median, mo (95% CI)6.17.97.37.1 (6.0-8.1)
     1-y survival rate26302729 (22-36)
     2-y survival rate21271624 (18-30)
    Refractory to second-line or greater therapy
     Deaths8892867785
     Median, mo (95% CI)6.64.75.36.16.1 (5.2-7.0)
     1-y survival rate299243026 (22-31)
     2-y survival rate196142217 (13-22)
    Relapse at 12 months post-ASCT or earlier
     Deaths9494868086
     Median, mo (95% CI)5.94.27.06.56.2 (5.2-7.6)
     1-y survival rate1925383432 (24-41)
     2-y survival rate66212619 (12-27)
    • Values shown as percentages, unless otherwise indicated. Hazard ratios (HRs) have been calculated from a Cox proportional hazards model (stratified by center). Second-line refractory vs primary refractory, HR, 1.24 (P = .17). Relapsed ≤12 months after ASCT vs primary refractory, HR, 1.20 (P = .17).

  • Table 4.

    Overall survival by patient subgroup

    Pooled (N = 636)
    Median OS, mo (95% CI)1-y OS rate, % (95% CI)2-y OS rate, % (95% CI)Hazard ratio* (P)
    Age
     <65 y6.3 (5.8-7.0)28 (24-32)20 (16-23)1 (reference)
     ≥65 y6.9 (4.9-9.5)30 (20-40)19 (11-29)0.9 (.37)
    ECOG PS
     0-16.5 (6.0-7.6)27 (22-33)21 (16-26)1 (reference)
     2+3.0 (2.0-4.3)15 (7-24)6 (2-14)2.1 (<.0001)
    Disease stage
     I-II8.7 (6.5-11.3)39 (29-49)31 (22-40)1 (reference)
     III-IV5.4 (4.3-6.2)20 (15-26)15 (10-20)1.8 (<.0001)
    IPI risk classification
     Low risk9.6 (7.4-16.6)44 (34-54)35 (26-45)1 (reference)
     Low-intermediate risk6.3 (5.2-8.2)22 (13-31)15 (8-24)1.8 (<.0001)
     High-intermediate to high risk3.8 (2.9-5.0)15 (9-23)10 (5-18)2.8 (<.01)
    • * Hazard ratio from a Cox proportional hazards model stratified by center.

    • Low risk, 0-1 points; low-intermediate risk, 2 points; high-intermediate to high risk, ≥3 points.