DLBCL

Bendamustine plus ofatumumab for naïve, elderly patients with DLBCL: Results from a phase II trial

On 9 May 2019, Ian Flinn from the Sarah Cannon Research Institute, Nashville, TN, USA, and colleagues, published diffuse large B-cell lymphoma (DLBCL) phase II clinical trial results (NCT01626352) in The Oncologist.1 This trial investigated the efficacy of bendamustine and ofatumumab in elderly patients with newly-diagnosed DLBCL, who were not good candidates for standard chemotherapy regimens.

The current standard of care for DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Nevertheless, old age has been associated with worse outcomes following R-CHOP in patients with DLBCL2. Bendamustine in combination with rituximab has shown a more tolerable safety profile in elderly patients than R-CHOP3. The anti-CD20 antibody ofatumumab, is also well-tolerated in this population and mediates B-cell lysis.4 Therefore, this trial sought to examine whether bendamustine plus ofatumumab could be an effective and well tolerated regimen for naïve and elderly DLBCL patients.

The primary endpoint of this single-arm trial was complete response (CR) rate. Secondary endpoints included, overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.

Study design & baseline characteristics
  • N = 21 enrolled patients with DLBCL, aged ≥ 70 years
  • Median patient age (range): 83 (73−88) years
  • Male patients: 42.9% (n = 9)
  • Dosing (21-day treatment cycles):
    • Bendamustine: 90 mg/m2 intravenously (IV) on Days 1 and 2 of cycles 1−6
    • Ofatumumab: 1000 mg IV on Days 1 and 8 of cycle 1 and on Day 1 of cycles 2−6
  • Modified Ann Arbor disease stage at diagnosis:
    • Stage III: 66.7% (n = 14)
    • Stage IV: 33.3% (n = 7)
  • Patient race:
    • White: 95.2% (n = 20)
    • American indian/Alaskan native: 4.8% (n = 1)
  • Median β2-microglobin levels (range): 3 (0−7)
  • Abnormal β2-microglobin levels: 85.7% (n = 18)
Key findings
  • Median follow-up (range): 9.9 (2.3−4) months

ORR, n (%)

19 (90.5%)

Complete response (CR)

7 (33.3%)

Partial response (PR)

12 (57.1%)

Stable disease (SD)

1 (4.8%)

Progressive disease (PD)

1 (4.8%)

Not evaluable

0

Median PFS (90% CI)

8.6 months (4.6−10.6)

Median OS (90% CI)

12.0 months (5.9−30.8)

Median time-to-progression (TTP; 90% CI)

10.5 months (4.5−not reached)

  • 12-month OS probability: 52.4% (90% CI, 33.4−3)
  • 12-month PFS probability: 31.7% (90% CI, 15.9−8)
  • 12-month TTP probability: 40.1% (90% CI, 19.1−4)
  • Patients who completed treatment: 57.1% (n = 12)
  • Reasons for treatment discontinuation:
    • PD: 14.3% (n = 3)
    • Concurrent illness: 9.5% (n = 2)
    • Death: 9.5% (n = 2; one treatment-related bowel sepsis and one from unknown cause)
    • Patient request: 4.8% (n = 1)
    • Non-compliance: 4.8% (n = 1)
  • The study was discontinued early on due to low patient accrual
Safety
  • Hematological Grade ≥ 3 adverse events (AEs) that occurred:
    • Thrombocytopenia: 14% (n= 3)
    • Neutropenia: 10% (n= 2)
    • Leukopenia: 5% (n = 1)
    • Anemia: 5% (n = 1)
    • Lymphopenia: 5% (n = 1)
  • Non-hematological Grade ≥ 3 AEs observed:
    • Vomiting: 10% (n = 2)
    • Diarrhea: 5% (n = 1)
    • Necrosis: 5% (n = 1)
    • Hypomagnesemia: 5% (n = 1)
    • Hyperuricemia: 5% (n = 1)
    • Sepsis: 5% (n = 1)
    • Anorexia: 5% (n = 1)
    • Fatigue: 5% (n = 1)
    • Pneumonia: 5% (n = 1)
    • Hypocalcemia: 5% (n = 1)
    • Hypokalemia: 5% (n = 1)
    • Tumor lysis syndrome: 5% (n = 1)
  • Patient deaths at follow-up: 66.7% (n = 14)
    • Reasons of death:
      • Due to AE: 4.8% (n = 1; bowel necrosis)
      • Due to disease: 28.6% (n = 6)
      • Due to concurrent illness: 4.8% (n = 1)
      • Due to unknown causes: 28.6% (n = 6)
Conclusions

The results of this small phase II trial showed that the combination of ofatumumab and bendamustine was well tolerated and led to modest response rates in elderly, newly-diagnosed patients with DLBCL. The degree of efficacy may appear modest when compared to standard of care, but maybe of benefit to those intolerant to R-CHOP.

References
  1. Flinn I.W. et al. Phase II Study of Bendamustine and Ofatumumab in Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy. Oncologist. 2019 May 9. pii: theoncologist.2019-0286. DOI: 10.1634/theoncologist.2019-0286 [Epub ahead of print].
  2. Weidmann E. et al. Phase II study of bendamustine in combination with rituximab as first-line treatment in patients 80 years or older with aggressive B-cell lymphomas. Ann Oncol 2011; 22:1839–1844. DOI: 10.1093/annonc/mdq671 [Epub 2011 Jan 21].
  3. Smith S.D. et al. 2013. Diffuse large B-cell lymphoma in adults aged 75 years and older: a single institution analysis of cause-specific survival and prognostic factors. Ther. Adv. Hematol. 4, 349–53. DOI:10.1177/2040620713505048
  4. Li B. et al. 2009. Characterization of a rituximab variant with potent antitumor activity against rituximab-resistant B-cell lymphoma. Blood 114, 5007–15. DOI:10.1182/blood-2009-06-225474
Download this article:

You can now download this article in Adobe PDF® format.

Download as PDF
Was this article informative? Thank you for your feedback!
100% of people found this article informative