Plinabulin and Pegfilgrastim in Combination for the Prevention of Chemotherapy-Induced Neutropenia in Patients with Breast Cancer (PROTECTIVE-2): A Randomized Trial

PurposePlinabulin is a non-granulocyte colony-stimulating factor (G-CSF) novel small molecule with both anticancer and myeloprotective effects. Single-agent plinabulin is myeloprotective in the first week of the chemotherapy cycle, and pegfilgrastim in the second week. We assessed the efficacy and safety of the combination of plinabulin and pegfilgrastim for the prevention of chemotherapy-induced neutropenia (CIN) following chemotherapy.MethodsThis randomized, open-label, Phase 2 trial enrolled patients with breast cancer. All received docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 on Day 1. In the combined therapy cohort, patients received plinabulin 20 mg/m2 on Day 1 and 1.5, 3, or 6 mg pegfilgrastim on Day 2. The primary objective was to establish the recommended Phase 3 dose (RP3D). Secondary endpoints included absolute neutrophil count (ANC) nadir, relative dose intensity (RDI), and incidence of adverse events including neutropenia and bone pain.ResultsIn total, 115 patients were randomized and evaluated. The combination therapy at the RP3D (plinabulin 20 mg/m2 and pegfilgrastim 6 mg) was well-tolerated and had superior CIN prevention in terms of Grade 4 and Grade 3/4 neutropenia frequency, absolute neutrophil count (ANC) nadir, higher relative dose intensity (RDI), less bone pain, and less toxicity burden when compared with pegfilgrastim 6 mg alone.ConclusionPlinabulin combined with pegfilgrastim at the RP3D (plinabulin 20 mg/m2 Day 1 and pegfilgrastim 6 mg Day 2) had more favorable efficacy, safety, and tolerability profiles and lower bone pain incidence than did pegfilgrastim alone.Trial information Clinical Trial Registration: ClinicalTrials.gov NCT04227990Date registered: January 14, 2020 Retrospectively registered

A Pilot Study of Cancer-Induced Bone Pain Using Validated Owner Questionnaires, Serum N-Telopeptide Concentration, Kinetic Analysis, and PET/CT

Cancer-induced bone pain, despite its frequency and severity, is a poorly understood phenomenon in people and animals. Despite excitement regarding translational osteosarcoma studies, there is a lack of attention toward examining cancer pain in dogs. In this pilot study, we used a multimodal pain assessment methodology to evaluate pain relief after therapeutic intervention in dogs with primary bone cancer. We hypothesized that intervention would cause objective evidence of pain relief. Evaluations of 8 dogs with primary bone cancer included 18F-FDG PET/CT scans, kinetic analysis, validated owner questionnaires (Canine Brief Pain Inventory, canine BPI), and serum N-telopeptide (NTx) concentration. Dogs were routinely staged and had 18F-FDG PET/CT scans prior to treatment with day 0, 7, 14, and 28 canine BPI, serum NTx, orthopedic exam, and kinetic analysis. Dogs treated with zoledronate and radiation underwent day 28 18F-FDG PET scans. All clinical trial work was approved by the University of Missouri IACUC. Four dogs underwent amputation (AMP) for their appendicular bone tumors; four received neoadjuvant zoledronate and hypofractionated radiation therapy (ZOL+RT). Canine BPI revealed significant improvements in pain severity and pain interference scores compared to baseline for all dogs. Positive changes in peak vertical force (+16.7%) and vertical impulse (+29.1%) were noted at day 28 in ZOL+RT dogs. Dogs receiving ZOL+RT had a significant (at least 30%) reduction in serum NTx from baseline compared to amputated dogs (p = 0.029). SUVmax (p = 0.11) and intensity (p = 0.013) values from PET scans decreased while tumor uniformity (p = 0.017) significantly increased in ZOL+RT-treated tumors; gross tumor volume did not change (p = 0.78). Owner questionnaires, kinetic analysis, and 18F-FDG PET/CT scans showed improved pain relief in dogs receiving ZOL+RT. Serum NTx levels likely do not directly measure pain, but rather the degree of systemic osteoclastic activity. Larger, prospective studies are warranted to identify the ideal objective indicator of pain relief; however, use of multiple assessors is presumably best. With improved assessment of pain severity and relief in dogs with cancer, we can better evaluate the efficacy of our interventions. This could directly benefit people with cancer pain, potentially decreasing the amount of subtherapeutic novel drugs entering human clinical trials.

Osteomyelitis infection disguised as Reiter’s Syndrome in a child: A case report

This is a case of a 16-year-old African boy with Osteomyelitis presenting with symptoms of reactive arthritis (Reiter’s syndrome) KEYWORDS Osteomyelitis, Reiter’s syndrome, Fever, Bone pain, Erythema, Ewing sarcoma

Development and Content Validity of a Novel Myelodysplastic Syndromes Symptom Daily Diary

Background Myelodysplastic syndromes (MDS) are associated with the reduction in healthy blood cells produced in the bone marrow, which subsequently lead to a variety of symptoms. A review of existing patient-reported outcome (PRO) questionnaires used in MDS or acute myeloid leukemia found that few if any were developed to measure symptoms of higher-risk MDS in the context of clinical trials. An MDS symptom daily diary has been developed following conduct of a targeted review of peer-reviewed literature and advice meetings with three clinical experts who treat patients with higher-risk MDS. The primary goal of this study was to evaluate the content validity of the novel MDS symptom daily diary among adults with higher-risk MDS. Methods Qualitative interviews were conducted via telephone with 15 adults with higher-risk MDS. The interviews were composed of two parts. During the concept elicitation portion, participants were asked to spontaneously describe their experience of higher-risk MDS, with particular focus on the symptoms they experience and the impact on their lives. Participants then completed the MDS symptom daily diary and provided feedback on the instructions, items, and response options in order to evaluate its readability, comprehensibility, relevance, and comprehensiveness. Interviews were conducted in three waves. Following each wave, developers reviewed summaries of results based on detailed interviewer notes. Revisions to the daily diary were made based on interim results prior to the next wave of interviews. Following the completion of all interviews, audio-recordings of the interviews were transcribed, coded, and analyzed. Results A total of 15 participants (53.3% female, ages 36 - 81 [mean=66, standard deviation=11.3] years) completed an interview: 7 in Wave 1, 3 in Wave 2, and 5 in Wave 3. All had begun treatment with a hypomethylating agent within six months prior to screening or were treatment-naïve. Participants reported experiencing 20 different symptoms of higher-risk MDS; the most frequently reported symptoms were fatigue (n = 13, 86.6%), bruising (n = 11, 73.3%), shortness of breath (n = 11, 73.3%), lack of energy (n = 10, 66.6%), heaviness in the arms or legs (n = 9, 60.0%), weakness (n = 9, 60.0%), bleeding (n = 8, 53.3%), and bone pain (n = 4, 26.6%). Participants identified fatigue and lack of energy as the most bothersome symptoms and the most important to improve with treatment. Based upon participant feedback in Wave 1, two items were removed from the draft diary due to their overlap with other items. Additionally, one item was revised for clarity. Following Wave 2, a single item to assess shortness of breath was retained while alternate items assessing shortness of breath were removed based on participant feedback. No further revisions to the diary were made based on participant feedback in Wave 3. The final version of the MDS symptom daily diary consists of eight items assessing fatigue, weakness, lack of energy, shortness of breath, bruising, bleeding, bone pain, and heaviness in arms or legs. All participants interpreted the instructions, items, and response options as intended by the developers. Participants found the diary easy to complete and relevant to their experience, and no participants suggested removing any items from the final version. Conclusion The MDS symptom daily diary has been developed as a tool to characterize the symptom burden of MDS and to evaluate the efficacy of study medications in clinical trials. The qualitative interviews provide evidence of its content validity; in future research, the psychometric properties of the daily diary and interpretation of its scores will be evaluated using data from an upcoming Phase 3 clinical trial. Disclosures Vallow: Novartis Pharmaceuticals: Current Employment. Brandt: Novartis Pharmaceuticals: Current Employment.

A Case Report on Symptom Improvement in a Polycythemia Vera Patient Treated with Acupuncture

Objectives: This study investigated the effectiveness of acupuncture for improving polycythemia-vera-related symptoms and quality of life.Methods: A 56-year-old woman diagnosed with polycythemia vera received acupuncture treatment between February 19, 2021, and August 26, 2021. We observed the changes in subjective symptoms and conducted myeloproliferative neoplasm symptom assessment form total symptom score (MPN-SAF TSS) questionnaire.Results: After 13 acupuncture treatment sessions over six months, symptoms of polycythemia vera, such as fatigue, bone pain, itching, and headache, improved.Conclusion: This study suggests that acupuncture may be a helpful treatment strategy for polycythemia vera patients suffering from significant symptom burdens and reduced quality of life.