Immune priming with avelumab and rituximab prior to R-CHOP in diffuse large B-cell lymphoma: the phase II AvR-CHOP study.

Immune evasion, due to abnormal expression of programmed-death ligands 1 and 2 (PD-L1/PD-L2), predicts poor outcomes with chemoimmunotherapy in diffuse large B-cell lymphoma (DLBCL). Immune checkpoint inhibition (ICI) has limited efficacy at relapse but may sensitise relapsed lymphoma to subsequent chemotherapy. ICI delivery to immunologically intact patients may thus be the optimal use of this therapy. In the phase II AvR-CHOP study, 28 patients with treatment-naive stage II-IV DLBCL received sequential avelumab and rituximab priming ("AvRp;" avelumab 10 mg/kg and rituximab 375 mg/m2 2-weekly for 2 cycles), R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone for 6 cycles) and avelumab consolidation (10 mg/kg 2-weekly for 6 cycles). Grade 3/4 immune-related adverse events occurred in 11%, meeting the primary endpoint of a grade ≥3 irAE rate of <30%. R-CHOP delivery was not compromised but one patient ceased avelumab. Overall response rates (ORR) after AvRp and R-CHOP were 57% (18% CR) and 89% (all CR). High ORR to AvRp was observed in primary mediastinal B-cell lymphoma (67%; 4/6) and molecularly-defined EBV-positive DLBCL (100%; 3/3). Progression during AvRp was associated with chemorefractory disease. Two-year failure-free and overall survival were 82% and 89%. An immune priming strategy with AvRp, R-CHOP and avelumab consolidation shows acceptable toxicity with encouraging efficacy.

Predicting primary treatment failure using interim FDG-PET scanning in diffuse large B-cell lymphoma.

Interim FDG-PET (iPET) in diffuse large B-cell lymphoma (DLBCL) is increasingly practised and used in clinical trials to adapt further therapy. However, the optimum timing and methodology of iPET remains controversial. We retrospectively analysed the iPET results and outcomes of 200 DLBCL patients where FDG-PET was routinely performed at baseline, after 2 cycles (iPET2) and at completion of chemoimmunotherapy. iPET was also performed after 4 cycles (iPET4) where at iPET2, Deauville score (DS) was ≥4. Scans were assessed by blinded expert lymphoma PET physicians for DS, maximum standard uptake value (SUVmax), total metabolic tumour volume (TMTV) and total lesion glycolysis (TLG). Treatment failure was defined as death, progression or refractory disease. 95.5% of patients received R-CHOP. No baseline PET parameter was predicted for EFS or OS independent of the NCCN-IPI. The multivariable analysis at iPET2 showed DS5 (19.5% of cases) predicted treatment failure (HR 6.29, 95% CI 3.01-13.17, P < .001), but DS4 was equivalent to DS1-3. At iPET4, ΔSUVmax < 66% predicted treatment failure (HR 5.49, 95% CI 3.03-9.99, P < .001). By multivariable analysis of all time points, high NCCN-IPI and DS5 at iPET2 were negative predictors of survival. These findings were independent of novel prognostic markers.

The IHC4+C score: an affordable and reproducible non-molecular decision-aid in hormone receptor-positive breast cancer. Does it still hold value for patients in 2020?

AIM: The majority of women diagnosed with early breast cancer have hormone-receptor positive (HR+)/HER2-negative disease. Adjuvant endocrine therapy provides substantial risk reduction benefits in virtually all patients. The role of adjuvant chemotherapy in certain subsets of patients is equivocal. This paper sought to evaluate the role of the IHC4+C score to aid this clinical decision in addition to providing an overview of the current molecular and non- molecular tools available in the adjuvant setting. METHODS: This prospective study included 53 post-operative HR+/HER2- negative early breast cancer patients selected from the multidiscipliniary team meeting between August 2017 and January 2020. IHC4+C testing was requested by clinicians for patients in whom the availability of the score may have impacted adjuvant decision-making. Adjuvant treatment decisions were recorded at three time points (prior and post IHC4+C scoring as well as the patient's final decision). The primary goal was the proportion of patients who were spared chemotherapy following the availability of IHC4+C scores to impact on clinicians' recommendations for adjuvant systemic therapy. RESULTS: A total of 34 patients (64%) were initially recommended to undergo chemotherapy or to consider chemotherapy. With the availability of the IHC4+C score, only 17 patients (32%) underwent chemotherapy, demonstrating a substantial reduction in the frequency of chemotherapy prescribing. CONCLUSION: This study demonstrates that when utilized appropriately in a multidisciplinary setting, the IHC4+C algorithm is an alternative, reproducible and affordable tool with a proven capacity to stratify risk and to spare a large proportion of patients from undergoing chemotherapy.