Outcomes of Richter's transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): an analysis of the SEER database.

Richter's transformation (RT) is a rare complication arising in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and is associated with an overall dismal outcome. The rarity of this entity poses many challenges in understanding its biology and outcomes seen and the optimal treatment approach. We utilized the SEER (Surveillance, Epidemiology and End Results) database to identify patients diagnosed with CLL/SLL between 2000 and 2016 and subsequently had a diagnosis of diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL), thus capturing those who experienced an RT event. We compared the outcomes of those patients to those of patients in the database diagnosed with DLBCL without a preceding CLL/SLL diagnosis. We identified 530 patients who developed RT out of 74,116 patients diagnosed with CLL/SLL in the specified period. The median age at RT diagnosis was 66 years, and the median time from CLL/SLL diagnosis to RT development was roughly 4 years. Patients with RT had a dismal outcome with median overall survival of 10 months. We identified advanced Ann Arbor stage (III/IV) and prior treatment for CLL as predictors of worse outcome in patients with RT. Our study represents the largest dataset of patients with CLL/SLL and RT and adds to the existing literature indicating the poor outcomes for those patients.

Evolution of Treatment Paradigms in Newly Diagnosed Multiple Myeloma.

The plasma cell neoplasm multiple myeloma (MM) is currently considered incurable. However, significant advances in treatment options over the past 20 years have led to unprecedented response rates to initial therapy as well as prolonged survival rates. Induction regimens have evolved from alkylator-based therapies to those consisting of immunomodulatory drugs and proteasome inhibitors. The combination of bortezomib/lenalidomide/dexamethasone (VRd) has emerged as a standard regimen for both transplant-eligible (TE) and transplant-ineligible (TI) patient populations. More recent efforts have focused on the incorporation of monoclonal antibody therapy into the newly diagnosed setting, particularly anti-CD38 monoclonal antibodies. In the TI patient population, the combination of daratumumab/lenalidomide/dexamethasone is now considered another standard therapy. In the TE setting, it remains to be determined whether the addition of daratumumab to the VRd backbone results in improved long-term outcomes. Recent studies have confirmed the progression-free survival benefit of upfront autologous stem cell transplant and have established lenalidomide maintenance as a standard of care. Multiple studies are evaluating whether inclusion of monoclonal antibody therapy in the maintenance setting will improve outcomes. The optimal management of newly diagnosed patients with high-risk cytogenetics remains to be determined. We discuss the emerging therapies that will likely shape management of newly diagnosed MM in the future.

Treatment Considerations for Transplant-Ineligible Multiple Myeloma.

While significant advances have been made in the treatment of multiple myeloma, the management of the transplant-ineligible (TI) patient population remains challenging. The individuals enrolled in clinical trials for newly diagnosed TI patients, or those with no planned transplant, may not always be reflective of real-world patients, with respect to age, comorbidities, or frailty status. Likewise, results obtained from randomized relapsed/refractory studies also may not be applicable to this generally older and frailer patient population. In this review, we discuss assessment of frailty and focus on treatment options in both the newly diagnosed and relapsed/refractory settings for TI patients. We describe the patient-specific considerations that factor into treatment decisions as well as provide some guidance about management.

Recurrent Catecholamine-Induced Cardiomyopathy and Hypertensive Emergencies: A presentation of Pheochromocytoma and Related Concerns.

Catecholamine-induced cardiomyopathy (CIC) and pheochromocytoma are both rare entities, and their exact incidence and prevalence are unknown. Pheochromocytoma has been implicated as one of the causes of CIC or Takotsubo syndrome (TTS) by means of case reports and retrospective reviews. However, the evaluation of any patient with TTS and pheochromocytoma is often faced with multiple challenges due to its rarity and atypical presentations, which subsequently leads to delay in diagnosis. Here, we present a case of a 51-year old female who had three distinct episodes of TTS and now presented in a hypertensive emergency with angina, palpitations, headache, nausea, and vomiting. She was treated for non-ST elevation myocardial infarction (NSTEMI) but coronary angiogram revealed patent coronary arteries. Due to the paroxysmal nature of her hypertensive emergencies and variable blood pressure response, pheochromocytoma was suspected. On further evaluation, she was found to have elevated metanephrines and a 6.3 cm left adrenal mass on CT scan. This case emphasizes the importance of considering or identifying pheochromocytoma as an underlying primary etiology for recurrent episodes of TTS and related concerns such as choice of anti-hypertensive agents.

Toxicities of Immune Checkpoint Inhibitors: Itis-Ending Adverse Reactions and More.

Immune checkpoint inhibitors (ICI) have revolutionized the treatment of cancer worldwide. Not long ago, before the introduction of ICIs, many cancers incurred a grave prognosis on patients due to the lack of effective therapies. For instance, patients with malignant melanoma survive longer and experience a better quality of life than ever before due to agents such as nivolumab and ipilimumab. Nevertheless, toxicities associated with the use of ICIs have been increasingly recognized in clinical trials as well as oncology practice. The widespread usage of ICIs and the expected addition of newer ICIs to the arsenal of medications to fight cancer raise awareness of the potential toxicities of these medications. Once these toxicities develop, immunosuppression with or without withholding immunotherapy is the standard of care. Because the long-term adverse effects of these toxicities and the impact of stopping therapy on survival are not well characterized, a joint decision by both the oncologist and the patient should be carried out if stopping therapy is being considered. Nevertheless, long-term data is necessary to guide such decisions. In this article, we will discuss common ICI's immune-related adverse events with a simplified approach to recognizing and managing these events.

Rapid onset type-1 diabetes and diabetic ketoacidosis secondary to nivolumab immunotherapy: a review of existing literature.

Nivolumab is a programmed cell death receptor (PD-1) inhibitor that is increasingly used for various malignancies, both as a first line agent and as salvage therapy. Being a PD-1/PD-1 ligand checkpoint inhibitor, it is known to cause autoimmune inflammation of various organs and has been associated with thyroiditis, insulitis, colitis, hepatitis and encephalitis to name a few. There are increasing reports of nivolumab leading to acute onset fulminant type 1 diabetes and diabetic ketoacidosis (DKA). We present a case of a 68-year-old man who developed DKA after 2 doses of nivolumab for metastatic melanoma. He was found to have type 1 diabetes, but no diabetes related antibodies were positive. He recovered from diabetes and continues to use insulin 1 year after his diagnosis. This case and associated review illustrates the importance of educating and monitoring patients who start nivolumab therapy regarding this potentially life threatening complication.

Finding the right BCR-ABL1 tyrosine kinase inhibitor: a case report of successful treatment of a patient with chronic myeloid leukemia and a V299L mutation using nilotinib.

BACKGROUND: Chronic myeloid leukemia can be effectively treated with BCR-ABL1 tyrosine kinase inhibitors. However, BCR-ABL1 mutations can develop and cause secondary resistance to these inhibitors. For each of the available BCR-ABL1 inhibitors, certain mutations are known to be associated with resistance, although most mutations that confer resistance to one tyrosine kinase inhibitor remain sensitive to one or more of the other available inhibitors. For patients displaying poor response or loss of response to frontline treatment, the possibility that they have developed a new BCR-ABL1 mutation must be considered, and selection of a second-line treatment must consider the patient's mutational profile. Here we describe a case in which a patient developed a V299L mutation; although this mutation is known to be associated with resistance to dasatinib while remaining sensitive to nilotinib, limited information is currently available regarding the use of second-line nilotinib following development of a V299L mutation while receiving dasatinib. CASE PRESENTATION: A 73-year-old man presenting with fatigue and drenching night sweats lasting for 2 weeks was diagnosed with chronic myeloid leukemia based on an analysis of a bone marrow biopsy and detection of the BCR-ABL1 fusion gene in peripheral blood. The patient initiated frontline treatment with dasatinib. A good treatment response was seen initially, with a complete hematologic response by month 2 of treatment. By month 20 however, BCR-ABL1 transcript levels rose markedly, and a mutational analysis revealed a BCR-ABL1 V299L mutation. Based on the identification of this specific mutation, the patient switched treatment to nilotinib; by month 18 of nilotinib treatment, the patient achieved a deeper reduction in BCR-ABL1 transcript levels than was seen with dasatinib. To date, in month 34 of treatment with nilotinib, the patient has shown good tolerance of the drug and has no clinical evidence of disease progression. CONCLUSIONS: Our case report illustrates the benefit of having multiple drugs available to treat chronic myeloid leukemia, each with the ability to inhibit a distinct set of BCR-ABL1 mutations. This patient's case suggests that switching to nilotinib can be an effective treatment option for patients who develop a BCR-ABL1 V299L mutation while receiving dasatinib.