Reader Responses: What is the best consolidation therapy for this patient with primary central nervous system lymphoma?

Here’s how readers responded to a You Make the Call question about the treatment of primary central nervous system lymphoma.

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Based on the two randomized trials (IELSG32 and PRECIS) comparing autologous hematopoietic cell transplantation (AHCT) with consolidative whole brain radiotherapy (RT) in PCNSL, I favor thiotepa-based AHCT, primarily because of the ability to avoid whole brain RT with AHCT and thus preserve neurocognitive function. However, there are caveats, and it’s a risk/benefit decision for each patient. Considerations include:

  1. Efficacy. In those randomized trials, there was no advantage to either arm in terms of efficacy. Progression-free survival (PFS) was similar in both arms.
  2. Toxicity with transplant. Transplant-related mortality was 6% in IELSG32 and 11% in the transplant arm of PRECIS, which is very concerning and much higher than we see with either whole brain RT or AHCT approaches in practice.
  3. Toxicity with whole brain RT. This is the main reason to favor AHCT, i.e., to avoid whole brain RT and the neurocognitive decline that can happen afterward. However:

a) the whole brain RT dose used in those trials (36 Gy in IELSG32 and 40 Gy (!) in PRECIS) are higher than many U.S. radiation oncologists use (typically in the range of 23-30 Gy), and
b) there is now evidence that memantine may attenuate the cognitive decline seen in patients undergoing whole brain RT.

For these reasons, the difference in neurocognitive decline seen in IELSG32 and PRECIS likely would be less apparent or not seen at all with 23-30 Gy whole brain RT and memantine neuroprotection.

I think this is a very complicated question overall. Both are good options and can achieve 70-80% PFS at 2 years, which is much better than the results seen 10+ years ago.

Timothy Fenske, MD
Medical College of Wisconsin
Milwaukee, WI

I would recommend thiotepa-based high-dose therapy/AHCT.

Chieh-Lung Cheng, MD
National Taiwan University
Taipei, Taiwan

If the patient is in complete remission with induction treatment, I would recommend low-dose radiotherapy.

Michalis D Michael, MD, PhD
Nicosia, Cyprus

AHCT with thiotepa, busulfan, and cyclophosphamide (TBC) conditioning for fit patients or carmustine/thiotepa for elderly patients or those with a lower performance status score.

Yuliya Linhares, MD
Miami, FL

High-dose therapy with a thiotepa-conditioning regimen with AHCT rescue.

Lauren C. Pinter-Brown, MD, FACP
UC Irvine
Irvine, CA

High-dose chemotherapy and AHCT.

Umberto Vitolo, MD
Torino, Italy

High dose cytarabine-based therapy.

Bruce G. Raphael, MD
NYU Langone Health
New York, NY

I would recommend ibrutinib.

Allen Greenberg, MD
Davie, FL

I would recommend autograft with carmustine/thiotepa conditioning.

Luke Coyle, MBBS
Sydney, Australia