Trial Presents Promising New Treatment for Rare Lymphoma

IVLBCL is a rare subtype of lymphoma that is particularly hard to diagnose due to a lack of swelling or enlargement of the lymph nodes.

A phase 2 multicenter clinical trial found that more than 75% of participants with intravascular large B-cell lymphoma (IVLBCL) reached 2-year survival without disease progression when administered a new combination of drugs in addition to high-dose methotrexate and intrathecal chemotherapy.1

IVLBCL is a rare subtype of lymphoma that is particularly hard to diagnose due to a lack of swelling or enlargement of the lymph nodes. The disease tends to affect elderly patients, for whom standard high-dose chemotherapy may have serious adverse effects (AEs) and who are at high risk of developing subsequent central nervous system (CNS) disorders even with treatment.1

The rarity of the disease has made it difficult to investigate, according to a press release from Nagoya University, where the investigators are based. An earlier retrospective study found that patients who had undergone standard chemotherapy combined with rituximab had more promising outcomes than patients who received standard treatment alone, but that study did not tackle the issue of secondary CNS involvement.1

In an effort to develop a novel treatment protocol with fewer AEs and which also minimizes secondary CNS involvement, investigators administered rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone to 37 participants, in addition to high-dose methotrexate and intrathecal chemotherapy.2

“We considered that rituximab-containing chemotherapies combined with treatment for the secondary CNS problems could lead to further improvement in the clinical outcome,” said Kazuyuki Shimada, MD, in a statement.1

The participants were enrolled between June 16, 2011, and July 21, 2016, with a median follow-up of 3.9 years. Notably, 76% of the patients reached the primary goal of 2-year survival without disease progression and 92% reached 2-year overall survival. The disease affected the CNS in just 3% of the patients.2

“To the best of our knowledge, this is the first prospective trial of any treatment in patients with IVLBCL,” Shimada said. “It appears that the proposed treatment protocol might be effective in patients without apparent central nervous system involvement at the time of diagnosis.”1

Furthermore, the toxicity of the treatment was found to be low and all AEs were manageable, with very few serious complications, according to the press release.1

One significant advantage of the treatment protocol is that it uses a combination of conventional drugs and no novel agents, meaning that it could be adopted in clinical practice soon, although it still needs further research.1

“Given the rarity of the disease, a large-scale phase 3 prospective trial is not feasible,” Shimada concluded. “In such a scenario, the results of our trial provide a safe and effective treatment option that can function as a historic control for future prospective trials.”1


  • The fitht goes on: Clinical trial shows promising new treatment for rare blood cancer [news release]. Nagoya University; May 28, 2020. Accessed June 4, 2020.
  • Shimada K, Yamaguchi M, Atsuta Y, et al. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): a multicenter, single-arm, phase 2 trial. The Lancet Oncology; March 11, 2020. Accessed June 4, 2020.