A prospective study on early PET/CT scans during the first cycle of salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma

Abstract

Many patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will not respond to platinum-containing salvage chemotherapy. Predicting treatment failure earlier could help clinicians minimize chemotherapy toxicities for non-responders in favor of other treatments. We conducted a pilot study where 2 early PET/CTs were obtained on days 4 (D4) and 21 (D21) of cycle 1 (C1) of salvage therapy for DLBCL. Twenty-five patients were enrolled and have evaluable data. Ten (40%) had an unplanned therapy change after C1 and before end-of-treatment (EOT) evaluation due to treatment failure on early PET/CT as interpreted by the treating physician. Early PET/CT response at D4 or D21 was not associated with EOT response in evaluable patients. Disease specific survival was longer for patients with a persistent response on both D4 and D21 (p = 0.042). Early PET/CT may predict salvage chemotherapy failure and could inform future clinical trials investigating early therapy change to non-chemotherapy treatments.

Trial registration: ClinicalTrials.gov NCT02405078.

Keywords: Diffuse large B-cell lymphoma; end of treatment; positron emission tomography/computed tomography; real-time response assessment; salvage chemotherapy.

Conflict of interest statement

Disclosure of conflicts of interest

Authors not listed had no disclosures to report.

Figures

Figure 1.

Early PET/CT responses stratified by treatment decision and EOT response. Each flow represents an individual patient and is colored according to their end-of-treatment response. Patients continued the same therapy, changed to a new therapy, or stopped therapy for supportive measures after cycle 1 of salvage treatment. PET/CT non-response includes stable disease and progressive disease. *Patients missing an EOT PET/CT were categorized as clinical responders or non-responders here. Of the 2 clinical responders, 1 underwent early apheresis and autologous stem cell transplant before EOT after achieving a CR on D4 and D21 PET/CTs and 1 achieved a CR at EOT by CT imaging. Of the 7 clinical non-responders, 3 discontinued therapy after cycle 1 for supportive measures and 4 changed therapy after cycle 1 but had clinical or radiographic (CT) evidence of non-response to their next therapy. CR: complete response; PR: partial response; NR: non-response; NA: not available; D: day; PET/CT: positron emission tomography/ computed tomography; EOT: end-of-treatment

Figure 2.

Serial early PET/CT images from an individual patient who underwent early therapy change. This patient achieved a partial response by D4 of R-ICE salvage immunochemotherapy, however developed progressive disease by D20. They were immediately switched to R-DHAP and demonstrated a persistent complete response on a second set of early PET/CTs. After a second cycle of R-DHAP, they were still in a complete response (end-of-therapy). This patient proceeded to receive an autologous stem cell transplant. D: day; R-ICE: rituximab, ifosfamide, carboplatin, etoposide; PR: partial response; PD: progressive disease; R-DHAP: rituximab, dexamethasone, cytarabine, cisplatin; CR: complete response; EOT: end-of-therapy

Figure 3.

Disease specific survival from start of salvage immunochemotherapy for all patients (A) and according to response by visual assessment and ΔSUVmax cutoff of 50% on PET/CT from D4 (B-C) and D21 (D-E), respectively. D: day; PET: positron emission tomography; SD: stable disease; PD: progressive disease; CR: complete response; PR: partial response; SUVmax: maximum standardized uptake value.

Figure 4.

Disease specific survival from start of salvage immunochemotherapy for patients according to persistent response on D4 and D21 by visual assessment (A) and ΔSUVmax cutoff of 50% (B).