Bortezomib-induced motor neuropathy: A case report.

INTRODUCTION: Bortezomib is a proteasome inhibitor used in the treatment of multiple myeloma, Waldenström's macroglobulinemia, mantle cell lymphoma. The most reported adverse effects include fatigue, thrombocytopenia, gastrointestinal symptoms, and peripheral neuropathy, which mostly manifests as sensory neuropathic symptoms. We present a case of a patient who experienced motor neuropathy after initiating treatment with bortezomib. CASE REPORT: An 87-year-old male was diagnosed with multiple myeloma and started on treatment with bortezomib, dexamethasone, and lenalidomide (VRd). After five cycles of therapy, he developed lower extremity weakness, which was severely debilitating, affecting his ability to walk, and this prompted his visit to the emergency department. MANAGEMENT AND OUTCOME: The patient was admitted for further workup and underwent electromyography, which was consistent with demyelinating polyneuropathy with active denervation. His symptoms were attributed to bortezomib, and his VRd regimen was held. His symptoms failed to improve despite discontinuation of bortezomib. He then received steroids and intravenous immunoglobulin (IViG) with a gradual resolution of his symptoms. He was thereafter restarted on only lenalidomide and dexamethasone with no recurrence of his neuropathy. DISCUSSION: Clinicians need to be aware of the likely risk for motor neuropathy associated with bortezomib. Risk factors like older age and pre-existing neuropathy can predispose patients to this adverse effect, and clinicians should monitor for this toxicity and facilitate dose reduction or discontinuation of therapy if warranted. Sometimes, patients may also need further treatment with steroids or IVIG.

One-pot green synthesis of polymeric nanocomposite: Biodegradation studies and application in sorption-degradation of organic pollutants.

The research work proposes the synthesis of a nanocomposite hydrogel which is a dual combination of binary interpenetrating network (BIPN) and bismuth ferrite nanoparticles. BIPN synthesized from binary graft copolymer (BGC) used as starting material. The cross-linked network of BGC is interpenetrating the newly synthesized cross-linked network of poly(acrylic acid) and the product is named as BIPN. Binary graft copolymer had been synthesized from grafting of guggul aqueous extract with copolymeric chains of acrylamide (primary monomer) and acrylic acid (secondary monomer) crosslinked by N,N'-methylene bisacrylamide (MBA). The maximum percentage swelling was evaluated for BGC through optimization of various reaction parameters: amount of water, binary ratio of acrylamide to acrylic acid, concentrations of MBA, ammonium persulphate, pH, temperature and time. Considering pre-optimized parameters for BGC synthesis, BIPN formation required optimization of only acrylic acid. Maximum percentage swelling obtained was 1497.79% and 308.15% for BGC and BIPN, respectively. Maximum percentage biodegradation of 90.64% and 82.38% were calculated for BGC and BIPN, respectively using composting method. Degradation efficiency of brilliant blue (BB) and fuchsin basic (FB) dyes was in the order: Nanocomposite ≫ BIPN > BGC. Maximum percentage degradation observed in case of nanocomposite was 94.1% and 99.3% in sunlight for BB and FB, respectively. The interaction of dyes with the nanocomposite involved mainly ionic interactions. The adsorption models Freundlich and Langmuir were applicable to overall adsorption and degradation process of BB and FB, respectively. Maximum adsorption capacities corresponding to minimum concentration i.e. 10 mg L-1 for BB and FB were calculated as 0.409 mg g-1 and 0.439 mg g-1, respectively. Second order and first order kinetics were found to be suitable for BB and FB adsorption-degradation pathways, respectively. Intraparticle diffusion mechanism was favorable to both dyes and adsorption followed three steps. Gas chromatography coupled with mass spectrometric analysis could give the degraded products which was helpful in drawing degradation pathway. The degradation process involved active radical species (O2-., OH.) and they carry out oxidation-reduction reactions on dyes to give decolorized solution containing mineral ions.

Therapy-related peripheral neuropathy in multiple myeloma patients.

This review discusses the most common issues concerning multiple myeloma (MM)-related peripheral neuropathy (PN). This is an important MM complication, observed in up to 54% of newly diagnosed patients, caused by the disease itself or its treatment. Although its aetiology is largely unknown, a number of mechanisms are suspected. It is important to know the neurological status of a patient, as many new antimyeloma medicines can trigger or exacerbate any pre-existing neuropathy. Examples include thalidomide-induced and bortezomib-induced PN (TiPN and BiTN, respectively), which are key MM treatment options. TiPN is usually sensory and sensorimotor, whereas BiPN is typically sensory. The mechanisms of chemotherapy-induced neurotoxicity in MM are well known; thalidomide seems to induce PN through its antiangiogenic properties, whereas bortezomib neurotoxicity is connected with disrupted calcium homeostasis. TiPN incidence ranges from 25% to 75%, and its prevalence and severity appears to be dose-dependent. BiPN incidence is almost 40% and is dose-related as well. Poor (25%) reversibility of TiPN prompted the recommendations for dose and exposure reduction, whereas BiPN cases are mostly reversible (64%). Peripheral sensory neuropathy is very rare in patients receiving bendamustine monotherapy. Because of this favourable toxicity profile, bendamustine may be considered a promising option for combination therapies in pre-existing PN in myeloma patients. Considering the lack of curative therapy for treatment-emergent PN, prevention is a key management strategy in MM patients. All patients should be evaluated for PN before the administration of a neurotoxic drug, and those under treatment should be closely monitored by a neurologist.

Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence.

BACKGROUND: Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. CASE PRESENTATION: A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. DISCUSSION: CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. CONCLUSION: In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.