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7545
Background: Obinutuzumab (G)-chemotherapy (chemo) has demonstrated improved progression-free survival compared with rituximab (R)-chemo in previously untreated advanced follicular ...lymphoma (FL). G is currently administered by IV infusion over ̃3–4 hours. A shorter duration of infusion in Cycle (C) 2 and subsequent cycles, as is standard practice with R, could improve convenience for patients (pts) and efficiency for infusion facilities. We report the primary analysis of the prospective, open-label, multicenter, single-arm, Phase IV, GAZELLE study (NCT03817853), which evaluated the safety of G administered as a 90-minute (min) SDI from C2 onwards in pts with FL. Methods: Pts with previously untreated FL received G (1000mg) intravenously on Day (D) 1, 8, and 15 of C1, and on D1 thereafter, plus chemo (bendamustine, CHOP, or CVP) for 6–8 cycles. In C1, pts received G at the standard infusion rate. Pts without a Grade (Gr) ≥3 infusion-related reaction (IRR) in C1 were eligible to receive G as a 90-min SDI from C2. Pts with a Gr 3 IRR in C1 received the standard G infusion in C2, and were eligible for G SDI in subsequent cycles if no Gr ≥3 IRRs occurred. Pts with a second Gr 3/4 IRR discontinued G. At the end of induction (EOI), responding pts received maintenance G (1000mg) as SDI for 2 years or until disease progression (PD). The primary endpoint was incidence of Gr ≥3 IRRs during C2. IRRs were defined as any event occurring ≤24 hours from infusion judged to be related to treatment. Secondary endpoints included adverse events (AEs) and investigator-assessed overall response rate at EOI. Results: As of December 3, 2020, 113 pts had received study treatment. Median age was 62.0 years, 50.4% were male, 61.9% had stage IV FL, and 45.1% were classified as high-risk FLIPI. Of the 110 pts who were eligible for G SDI from C2, no pt experienced a Gr ≥3 IRR with SDI in C2 (Table). One pt experienced a Gr 3 IRR with SDI in C5, presenting hypertension. All other IRRs with SDI were Gr 1/2. No Gr 4/5 IRRs were reported. Other AEs were similar to those observed in previous studies. At the clinical cut-off date, 104 pts had a CT imaging-based response assessment at EOI and 9 pts had no response assessment; 76/113 (67.3%) had a complete response, 22 (19.5%) had a partial response, and six (5.8%) had PD. Conclusions: In GAZELLE, G SDI in C2 and beyond appeared to be safe. No Gr 3 IRRs were observed in C2 and only one Gr 3 IRR was reported in subsequent cycles. The safety profile of G SDI was comparable with the established profile of G in advanced FL. Clinical trial information: NCT03817853. Table: see text
7561
Background: PN is an identified risk of anti-microtubule agents, including polatuzumab vedotin and vincristine. POLARIX (NCT03274492), a Phase III randomized, double-blind, placebo-controlled ...study comparing Pola-R-CHP with R-CHOP, demonstrated improved progression-free survival (PFS) with Pola-R-CHP (Tilly et al. NEJM 2022). Here, we evaluate the impact of Pola-R-CHP vs R-CHOP on PN using ClinRO and PRO data. Methods: Patients with previously untreated diffuse large B-cell lymphoma (DLBCL) received Pola-R-CHP or R-CHOP. ClinRO data were based on PN grading according to the NCI CTCAE v4.0. PRO data were generated from assessment of patient-reported PN symptoms at baseline and Day 1 of each cycle using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity (FACT-GOG/NTX) subscale, ranging from 0–44, with higher scores representing lower levels of PN (minimal clinically important difference: 1.38–3.68 Cheng et al. Health Qual Life Outcomes 2020). Results: At baseline, ClinRO and PRO symptom scores showed low PN burden (Table). Overall incidence of PN was comparable between treatment arms (Pola-R-CHP: 52.9%; R-CHOP: 53.9%); most events were grade 1, and incidence of grade 2 (Pola-R-CHP: 12.2%; R-CHOP: 15.5%) and grade 3 (Pola-R-CHP: 1.6%; R-CHOP: 1.1%) events were comparable between treatment arms. FACT-GOG/NTX survey completion was high in both arms (96% at baseline; >80% at other timepoints). When evaluated by cycle, ClinRO and PRO demonstrated that more patients experienced earlier onset PN with R-CHOP than with Pola-R-CHP (Table), with ̃10% more R-CHOP- than Pola-R-CHP-treated patients having clinician-reported PN in Cycle (C) 2–5, and a ̃+1-point difference (i.e. fewer symptoms) in PRO symptom scores in C3–6 with Pola-R-CHP vs R-CHOP; by C8+, and during follow up, rates and symptoms of PN were similar. PN symptoms resulted in fewer dose reductions (3.9% vs 8.2%) and drug discontinuations (0.7% vs 2.1%) with Pola-R-CHP vs R-CHOP. Duration of PN was similar for both treatments. Conclusions: In the POLARIX study, Pola-R-CHP did not result in different rates or severity of PN vs R-CHOP. According to ClinRO and PRO data, PN occurred later following initial exposure to Pola-R-CHP than to R-CHOP, and there were fewer dose modifications with Pola-R-CHP than with R-CHOP. Overall, the risk of PN was manageable. Clinical trial information: NCT03274492. Table: see text
Abstract 5059
JAK2 inhibitors are known to improve symptoms, to control myeloproliferation and to reduce splenomegaly in patients diagnosed with chronic myeloproliferative neoplasms (MPNs)Ph(-). ...However their ability to decrease the allele burden and achieve molecular responses is controversial.
To evaluate hematologic, clinical and molecular responses according to the criteria of the European LeukemiaNet and European Myelofibrosis Network in 13 patients treated with JAK2 inhibitors.
We performed a prospective study in the Haematology Service of the Hospital La Pazbetween 1987 and 2012 in 13 patients diagnosed with NMP Ph (-) and treated with of JAK2 inhibitors: 5 secondary mylofibrosis (SFM)to homozygous polycythemia vera JAK (+), 4 SFM to essential thrombocythemias JAK (-), 2 primary myelofibrosis (one JAK (-) and one heterozygous JAK (+)) and 2 homozygous PV JAK (+) resistant to hydrea. The RT-PCR was performed at 6 or 12 months after the first determination of the allelic burden. Median follow-up was 3 months (1 – 15).
A) Hematologic Response (HR): 3/5 SFM to PV(1)/TE JAK(-)(2) reached HR at 3 months of initiation of JAK2 inhibitor to 20mg/day. Molecular and clinical response were not evaluated.
Three patients had a reduction in the spleen size. Only one patient in the SFM group had a reduction in the spleen size (18 cm before the drug was commenced to 13. 7 cm) and the allele burden decrease from 55% to 23% after 5 months of therapy with JAK2 inhibitor at 25mg/12h (increase of 5mg/12h after 15 days of initiation of medication). 2/3 MFS to TE JAK(-) had a reduction from 15, 3 cm before the drug was commenced to 9 cm after 3 months of therapy with JAK2 inhibitor at 20 mg/12h. 3/3 MFP JAK(-) had a 6cm reduction in spleen size. Twenty cm splenomegaly was documented before starting JAK2 inhibitor to 15 mg/day.
2/5 SFM to PV decreased the previous allele burden value. One patient decreased by 25% the previous allele burden value (99. 28%) at 6 months of JAK2 inhibitor. Second patient decreased by 13% the previous allele burden value (55%) at 6 months of starting JAK2 inhibitor to 25 mg/day. In 1/2 PV, the previous allele burden value (93. 17%) decreased by 11. 4% at 6 months of starting JAK2 inhibitor at 100mg/24h.
One patient with SMF secondary to JAK 2 (-) ET had dose reductions from 20 mg twice a day secondary to grade IV thrombocytopenia and renal toxicity. Patient finally developed acute leukemia.
Our study confirms that JAK2 inhibitors reduce splenomegaly in MPNs JAK(-)and JAK(+). Prospective studies with an adequate sample size are necessary to demonstrate whether splenomegaly and symptom reductions achieved with inhibition of JAK2 could be associated to decrease the allele burden and achieve molecular responses in MPNs JAK(+).
No relevant conflicts of interest to declare.
A 59-year old woman who attended the emergency department because of a bilateral peripheral facial nerve palsy (FNP). Bilateral FNP is uncommon, an idiopathic cause is unlikely and consequently a ...comprehensive study is indicated. An IgM monoclonal gammopathy was detected on serum protein electrophoresis of our patient. Bone marrow biopsy showed the presence of lymphoplasmocytoid cells. On the basis of these findings the diagnosis of Waldenström's macroglobulinemia (WM) was made. Secondary cranial nerve palsies are rarely seen in this condition. This report describes a case of bilateral FNP as initial presentation of a Waldenström's macroglobulinemia and discuss treatment.
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