ABSTRACT
Background: On 2019, the FDA and later the EMA granted approval to polatuzumab vedotin-piiq, a CD79b-directed antibodydrug conjugate indicated in combination with bendamustine and rituximab (P-BR) for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), after at least two prior therapies. P-BR has demonstrated (NCT02257567) better overall response rates (complete and partial responses) compared with BR alone (63% vs 25%) and response durations of at least 12 months in 48% of the patients. The most common adverse reactions with P-BR (incidence at least 20%) included cytopenias (most common reason for treatment discontinuation), peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite and pneumonia. Serious adverse reactions occurred in 64%, most often from infection. Aims: To analyze results in terms of efficacy and safety of the P-BR regimen in real life conditions. Methods: Observational, retrospective study in 3 academic centers. Adult patients (≥ 18 years old) diagnosed with DLBCL NOS R/R who received P-BR between July 2019 and December 2021 were included in the analysis. Results: 11 patients were treated with P-BR. The mean (SD) age was 70.1 (8.2) years (Range 57-81 years). Cell of origin was informed in 9/11 cases, 6 of them were activated B-cell (ABC) subtype. No double-/triple-hit lymphomas were confirmed. The median number of prior lines of therapy before P-BR was 2, with most patients (63%) refractory to the last treatment. All patients had received anti-CD20 (Rituximab) on prior treatments and only 2 (18%) Bendamustine. Baseline characteristics are shown in table 1. Efficacy Seven patients were evaluated by PET-CT after 3 cycles, 4 (57%) achieved CR and 3 PR (43%). Five patients achieved CR by PET-CT at the end of treatment. One of these patients is still in CR after 12 months of follow up and three of them after 24 months from the start of P-BR. One patient relapsed after 19 months. Of the patients achieving CR, all of them had responses >12 months. Only 3/5 completed the 6 cycles scheme, 1 patient received 5 cycles (treatment was interrupted due to an invasive fungal infection) and 1 patient received only 2 cycles as bridge therapy for and autoHCT and achieved CR after transplantation. 1 patient was refractory to treatment and progressed after 2 cycles. Toxicity: All patients were evaluated for toxicity. 63% (7/11) of them presented hematological toxicity, mainly neutropenia which required GCSF administration and 71% RBC transfusion. Two patients required hospital admission because of neutropenic fever. There were 3 documented cases of SARS-CoV-2 infection. Two patients had moderate disease with bilateral pneumonia (vaccinated) after the 2° cycle of treatment which is temporarily interrupted. One patient completed 6 cycles but died of severe SARS-CoV2 infection (unvaccinated) before being assessed for response at end of treatment. Two patients interrupted treatment definitely because of toxicity: severe cytopenia and invasive fungal infection. No other extra hematological toxicities were reported. Image: Summary/Conclusion: The P-BR regimen provides sustained good results for patients with R/R DLBCL who have failed treatment with prior therapies. Cytopenias were the most frequent form of toxicity and were easily addressed in most cases. In our experience, SARS-CoV2 infection has been a challenge due to delay in treatment and high morbidity and mortality.
ABSTRACT
INTRODUCTION: Guillain-Barré is an immune-mediated neurologic disorder in which myopathy, paralysis and even respiratory failure can occur. Typically, the antecedent is a bacterial or viral illness. In this case, the patient was suffering from SARS -COV 2, which was complicated by this rare and severe disease. METHODS: We have a case of a 53-year-old Hispanic male who presented to the hospital with four days of fevers and progressive shortness of breath. Given high suspicion of severe acute respiratory syndrome coronavirus 2 (SARSCOV 2), he underwent computed tomography scan which was consistent with atypical bilateral pneumonia. He would later be found positive for SARS-CoV 2 by reverse transcription polymerase chain reaction test. Other than hypoxia and coarse breath sounds throughout lung fields, physical exam was unremarkable. He was admitted to internal medicine and infectious disease was consulted. He was started on a five-day course of Remdesivir and a ten dose course dexamethasone. On day three, he began experiencing mild bilateral upper extremity weakness. Shortly thereafter his symptoms progressed to bilateral upper extremity paresis, descending paralysis, absent deep tendon reflexes, and respiratory failure requiring mechanical ventilation. Given patient history and physical exam findings there was a concern for Guillain-Barré which prompted neurology consultation. Nerve conduction study were performed which confirmed the diagnosis and the patient was treated with a five-day course of intravenous immunoglobulin (IVIG). His case was further complicated by Klebsiella aerogenes pneumonia which was treated with ceftriaxone. By day three of IVIG treatment, the patient was exhibiting 2/5 strength in upper extremities. Patient had significant improvement in motor strength of bilateral upper and lower extremities by day six with only reported numbness and tingling in his hands and was successfully extubated. He was transferred out of the critical care unit and was discharged from the hospital after three weeks with persistent paresthesia in upper extremities and mild dysphagia for which he was to receive outpatient speech therapy. RESULTS: Early recognition and treatment of Guillain-Barré as a sequela of SARS-CoV 2 is vital as delays could lead to severe disability or even death.