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Brentuximab vedotin followed by bendamustine supercharge for refractory or relapsed Hodgkin lymphoma

M. Picardi, R. Della Pepa, C. Giordano, N. Pugliese, C. Mortaruolo, F. Trastulli, M. G. Rascato, I. Cappuccio, M. Raimondo, M. Memoli, M. Monteverde, M. Mascolo and F. Pane

Article Figures & Data

Figures

  • Figure 1.

    Bv+Bs regimen schedule. Bv, at 1.8 mg/kg IV on day 1 of the 3-week cycle; Bs, at 120 mg/m2 IV on days 2 and 3 of the 3-week cycle; P, peg-filgrastim 6 mg subcutaneous on day 6 of the 3-week cycle; FDG-PET, at baseline and 5 weeks after salvage treatment completion; C, serum CMV-DNA monitoring on day 1 of the 3-week cycle. Moreover, as support prophylactic treatment: methylprednisolone at 200 mg IV on days 1 to 3 of the 3-week cycle, diphenhydramine at 50 mg IV on days 1 to 3 of the 3-week cycle, febuxostat at 80 mg orally on days 1 to 5 of the 3-week cycle (plus hyperhydration); trimethropin-sulfamethoxazole at 960 (160 + 800) mg orally every 12 hours 2 times a week and acyclovir at 800 mg orally daily from the start of Bv+Bs regimen until 1 month after the last cycle. Clinical visits were performed on days 1 to 3 of the 3-week cycle. Routine laboratory tests were performed every 2 weeks.

  • Figure 2.

    Bridge to transplant following Bv+Bs regimen. Autologous hematopoietic stem cell transplantation (ASCT; n = 14) was performed with PBSC previously harvested in 12 cases, or with post-Bv+Bs PBSC successfully collected (by G-CSF and cyclophosphamide) in 2 cases. Allogeneic hematopoietic stem cell transplantation (Allo-SCT; n = 4): haploidentical in 3 cases, and sibling in 1 case. Two patients received 2 additional courses of Bv+Bs (for a total of 6).

  • Figure 3.

    PFS. Kaplan-Meier curve of 2-year PFS of 20 patients with R/R cHL who received the Bv+Bs regimen (see “Patients and methods”). Table shows number of events and number at risk during follow-up.

  • Figure 4.

    Swimmers plot. Duration of patients’ response following Bv and Bs salvage treatment. Horizontal arrows denote ongoing response. Arrowheads (▾) denote radiation therapy. Circles (●) denote autologous HSCT. Rhombuses (♦) denote allogeneic HSCT. Squares (▪) denote 2 additional Bv+Bs courses. PR, partial remission; REF, refractory; REL, relapse.

Tables

  • Table 1.

    Baseline characteristics of analyzed patients

    Characteristicsn (%)
    Number of patients20
    Age
     Median (range), y40 (23-54)
    Sex
     Female12 (60)
     Male8 (40)
    Histological subtypes
     Nodular sclerosis16 (80)
     Mixed cellularity3 (15)
     Lymphocyte rich1 (5)
    Frontline therapy received
     ABVD, 4 courses5 (25)
     ABVD, 6 courses15 (75)
     Radiotherapy after ABVD6 (30)
    Response to frontline therapy
     Primary refractory11 (55)
     Relapsed
     CR ≤1 y5 (25)
     CR >1 y4 (20)
    Number of previous treatments
     25 (25)
     3-414 (70)
     >41 (5)
     Median (range)3 (2-6)
    Previous salvage therapy*
     IGEV16 (80)
     DHAP7 (35)
     Bv5 (25)
     BEACOPP1 (5)
     Radiotherapy1 (5)
    Transplant
     Autologous HSCT5 (25)
    At the time of Bv+Bs start
     Characteristics of disease
      ≥3 nodal sites involved12 (60)
      Extranodal involvement10 (50)
      Mediastinal bulky6 (30)
      Bone marrow involvement1 (5)
      LDH > normal limits7 (35)
      ESR >506 (30)
     Ann Arbor/Cotswold staging
      I-II6 (30)
      III-IV14 (70)
      B symptoms11 (55)
     ECOG-PS
      0-114 (70)
      ≥26 (30)
    • Values are n (%) unless otherwise noted.

    • ABVD, doxorubicin 25 mg/m2 IV on days 1 and 15, bleomycin 10 IU/m2 IV on days 1 and 15, vinblastine 6 mg/m2 IV on days 1 and 15, dacarbazine 375 mg/m2 IV on days 1 and 15; IGEV, ifosfamide 2000 mg/m2 IV on days 1 to 4, gemcitabine 800 mg/m2 IV on days 1 and 4, vinorelbine 20 mg/m2 IV on day 1, and prednisolone 100 mg orally on days 1 to 4; BEACOPP (escalated), bleomycin 10 UI/m2 IV on day 8, etoposide 200 mg/m2 IV on days 1 to 3, doxorubicin 35 mg/m2 IV on day 1, cyclophosphamide 1250 mg/m2 IV on day 1, vincristine 1.4 mg/m2 IV on day 8, procarbazine 100 mg/m2 orally on days 1 to 7, prednisone 40 mg/m2 orally on days 1 to 14; DHAP, cisplatin 100 mg/m2 by continuous IV infusion over 24 hours, followed by cytosine arabinoside IV in 2 pulses each at a dose of 2 g/m2 given 12 hours apart. Dexamethasone, 40 mg IV, was given on days 1 through 4; Bv, at a dosage of 1.8 mg/kg IV every 3 weeks for a median of 3 courses (range, 2-4); ECOG-PS, Eastern Cooperative Oncology Group–Performance Status; ESR, erythrocyte sedimentation rate; LDH, lactate dehydrogenase.

    • * Four patients received several lines of salvage therapy, before Bv+Bs regimen.

    • Stage I is defined as involvement of 1 nodal group or lymphoid organ; stage II is defined as involvement of 2 or more nodal groups on the same side of diaphragm; stage III is defined as involvement of nodal groups on both sides of the diaphragm; and stage IV is defined as disseminated involvement of 1 or more extralymphatic organs (eg, lung, bone) with or without any nodal involvement.