Cecal volvulus associated with carfilzomib use for al amyloidosis.

INTRODUCTION: Proteasome inhibitors have emerged as quintessential therapies for light-chain (AL) amyloidosis and multiple myeloma in the last decade. While these agents are highly effective, reports have also documented toxicities affecting various organ systems. Whereas gastrointestinal (GI) toxicities are a relatively common occurrence with proteasome inhibitors, severe GI complications are exceedingly rare. CASE REPORT: We describe a unique case of a patient with AL amyloidosis who developed cecal volvulus after four weeks of treatment with carfilzomib. This severe GI manifestation has not been previously described in the literature. MANAGEMENT AND OUTCOME: The patient required right hemicolectomy. After clinical recovery, she restarted reduced-dose carfilzomib. She did not have any severe GI side effects following dose reduction, and continues with the current treatment regimen to the present day. DISCUSSION/CONCLUSION: The causality between volvulus and the treatment with carfilzomib was probable, with a documented score of 6 on the Naranjo probability nomogram. The exact mechanism behind this effect of carfilzomib has yet to be elucidated.

Acute gout flare of bilateral first metatarsophalangeal joints due to ibrutinib use in chronic lymphocytic leukemia.

INTRODUCTION: Bruton tyrosine kinase inhibitors represent important tools in the therapeutic armamentarium against chronic lymphocytic leukemia (CLL) and other B-lymphoproliferative disorders. CASE REPORT: We describe herein a unique 65-year-old patient who presented with bilateral foot pain four months after starting treatment with ibrutinib for CLL. Of note, the patient had previously been diagnosed with gout, and was taking allopurinol prophylactically at the time of the event. Compliance with allopurinol was in excess of 99%. Yet, he was diagnosed with acute gout flare of bilateral first metatarsophalangeal (MTP) joints.Management & Outcome: Ibrutinib dose was reduced by one third, and the patient's gout flare up was treated with ibuprofen as needed. After symptoms abated, ibrutinib was continued at 2/3rds of the dose, with an excellent CLL control. The patient tolerated this dose without any further adverse effects.Discussion/Conclusions: We have reported a unique side effect of acute bilateral first MTP joint gout flare likely triggered by ibrutinib use for CLL while the patient was taking a xanthine oxidase inhibitor. The mechanism by which ibrutinib caused this phenomenon remains to be elucidated.

Sustained erythrocytosis due to the use of Lenvatinib.

INTRODUCTION: Tyrosine kinase inhibitors have become the mainstay of treatment for many malignancies, but their use can be accompanied by unusual and often puzzling side effects. CASE REPORT: We describe herein a 64-year-old patient who developed a robust and sustained erythrocytosis shortly after starting treatment with lenvatinib. Our patient also experienced elevated blood pressure, mucositis, and hand-foot syndrome that are not uncommonly seen with this agent. The clinico-laboratory work-up suggested that lenvatinib was the likely culprit in this case. MANAGEMENT & OUTCOME: Lenvatinib had to be discontinued due to suboptimal tolerance and a short-lived response. With the discontinuation of lenvatinib, hemoglobin trended downwards and subsequently resolved. A score of 6 on the Naranjo nomogram supported a probable causality relationship between lenvatinib and the observed erythrocytosis. DISCUSSION: Erythrocytosis has previously been described with sunitinub, sorafenib and pazopanib. The exact mechanism of this phenomenon is not known. It might increase the risk of venous and arterial thromboses in cancer patients that are already in a hypercoagulable state due to cancer itself. In addition, laboratory work-up for polycythemia may prove extensive and costly. Therefore, clinicians need to be aware of this important side effect of tyrosine kinase inhibitors.

Autoimmune hemolytic anemia in a patient with myelodysplastic syndrome: Responding to 5-azacitidine therapy.

INTRODUCTION: Autoimmune disorders, including autoimmune cytopenias, are more common in patients with myelodysplastic syndrome (MDS) and may share with MDS the same steps of pathogenesis. Some patients with MDS have antibodies against red cells. CASE REPORT: We describe herein a 79-year-old patient who presented with fatigue, jaundice and pancytopenia. She was diagnosed with warm-antibody autoimmune hemolytic anemia (AIHA) and synchronous MDS.Management and outcome: In our patient, AIHA responded to the hypomethylating agent 5-azacitidine used for the treatment of MDS. Six months later, the patient remains in clinico-laboratory remission for both MDS and AIHA. DISCUSSION/CONCLUSIONS: Our case indirectly suggests that 5-azacitidine led to a decrease in autoantibody production by the auto-reactive B-cell clone in MDS leading in turn to a diminished rate of autoimmune hemolysis. If our observation is accurate, we believe that similar reports will populate the scientific literature in the future years.

Multidirectional pattern of hair growth with carflizomib use for multiple myeloma.

INTRODUCTION: Extensive use of novel therapies for multiple myeloma has been accompanied by intriguing toxic side effects affecting various organs and organ systems. Although skin effects with some of these medications have been well-documented, hair changes are fairly rare. CASE REPORT: We report herein a unique case of a patient with myeloma who developed multidirectional pattern of scalp hair growth starting at 14 months into treatment with cafilzomib. This pattern of hair growth had not previously been described in the literature.Management and outcome: The patient had a near-complete response to caflizomib, and continues on this maintenance treatment regimen to the present day. There has not been any change in the unusual hair appearance and texture. DISCUSSION: A score of 5 on the Naranjo nomogram makes the causality relationship between carfilzomib use and the multidirectional hair growth probable. The mechanism by which carfilzomib causes this hair change remains to be elucidated.