Subsequent primary malignancies after diffuse large B-cell lymphoma in the modern treatment era

Br J Haematol. 2017 Jul;178(1):72-80. doi: 10.1111/bjh.14638. Epub 2017 May 25.

Abstract

With the addition of rituximab and other treatment advances, survival after diffuse large B-cell lymphoma (DLBCL) has improved, but subsequent primary malignancies (SPMs) have emerged as an important challenge for DLBCL survivorship. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPMs among 23 879 patients who survived at least 1 year after a first primary DLBCL diagnosed during 1989-2012, compared to the general population in California. Cumulative incidence (CMI) of SPMs, accounting for the competing risk of death, also was calculated. We found that the incidence of acute myeloid leukaemia (AML) nearly doubled in the post-rituximab era [SIR (95% CI) 4·39 (2·51-7·13) pre- (1989-2000) and 8·70 (6·62-11·22) post-rituximab (2001-2012)]. Subsequent thyroid cancer was rare pre-rituximab, but increased substantially after 2001 [0·66 (0·08-2·37) vs. 2·27(1·44-3·41)]. The 5-year CMI for all SPMs (4·77% pre- vs. 5·41% post-rituximab, P = 0·047), AML (0·15% vs. 0·41%, P = 0·003), thyroid cancer (0·03% vs. 0·15%, P = 0·003) and melanoma (0·25% vs. 0·42%, P = 0·020) were greater in DLBCL patients diagnosed in the post- versus pre-rituximab period. This study provides insight into the changing pattern of SPM occurrence after the introduction of rituximab, which may elucidate the aetiology of SPMs and should guide future cancer surveillance efforts among DLBCL patients.

Keywords: cancer; diffuse large B-cell lymphoma; incidence; lymphoma; second primary malignancy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • California / epidemiology
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Leukemia, Myeloid, Acute / chemically induced
  • Leukemia, Myeloid, Acute / epidemiology
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / epidemiology*
  • Male
  • Melanoma / chemically induced
  • Melanoma / epidemiology
  • Middle Aged
  • Neoplasms, Second Primary / chemically induced
  • Neoplasms, Second Primary / epidemiology*
  • Registries
  • Rituximab / adverse effects
  • Rituximab / therapeutic use
  • Thyroid Neoplasms / chemically induced
  • Thyroid Neoplasms / epidemiology
  • Young Adult

Substances

  • Antineoplastic Agents
  • Rituximab