Case Presentation: 53-Year-Old Patient With Progressive Myeloma After Multiple Lines of Therapy Case Presentation

Background:

53-year-old previously healthy female who initially presented to the emergency department with severe back and rib pain and serum studies revealed an elevated calcium level of 13mg/dL, creatinine of 2.1 mg/dL, and hemoglobin of 9.4 g/dL. Bone marrow biopsy showed 80% plasma cells and FISH was positive for t(11;14). Albumin was 3.8 g/dL, beta 2 microglobulin 5.9 mg/L, and LDH 1700 U/L. She was diagnosed with kappa light chain myeloma with a kappa light chain level of 11,154 mg/L.  Imaging showed extensive bony involvement and a T9 compression fracture, for which she had a T9 partial corpectomy. International staging system (ISS) and Revised International staging system (RISS) staging score was III.  She was started on treatment with cyclophosphamide, dexamethasone, and bortezomib.  She received two cycles of this regimen and achieved a very good partial response. She then started treatment with carfilzomib, lenalidomide, and dexamethasone and achieved a stringent complete response after 4 cycles. She next received an autologous stem cell transplant with melphalan chemotherapy preparative regimen and achieved a stringent complete response and MRD negativity. She was on lenalidomide maintenance for 2 years and then had progressive disease. She went on to receive two more lines of therapy, progressed after each line, and then was changed to teclistamab, a bispecific antibody therapy.

Presentation of Symptoms:

During Cycle 9 of teclistamab, she presented to the emergency department with worsening shortness of breath and was found to be hypoxic with an oxygen saturation of 89% on room air.  She had first started noticing dyspnea on exertion 3 weeks prior to presenting to the ED. She is an avid runner and had to stop multiple times due to shortness of breath, which was abnormal for her. Symptoms had worsened to the point of having dyspnea on exertion when she walked around the house and she also had a new and worsening cough, which prompted her to go to ER. CT chest imaging showed new extensive bilateral ground glass opacities predominantly involving the bilateral lower lobes; no evidence of pulmonary embolism. Neutrophil count was 1.09 X 10E9/L and dropped to as low as 0.21 X 10E9/L over the next several days.  Additionally, she was noted to have an IgG level of 141 mg/dL, as she was not able to make it to her previous appointments for intravenous immune globulin (IVIG).  While in the ED, she also complained of new onset diarrhea and stool samples sent were positive for a Clostridium difficle (C diff) infection (gene and protein positive) and Norovirus infection.

Management and Follow Up:

She was initially started on antibiotics with ceftriaxone and azithromycin in the ER.  She was admitted to the hospital and subsequently advanced to cefepime/azithromycin for fevers. She was given growth factor with GCSF to manage the neutropenia. She received a dose of IVIG while hospitalized. Pulmonary and infectious disease teams were consulted. Notably, the patient was on pneumocystis jirovecii pneumonia (PJP) prophylaxis with atovaquone (has Septra allergy) but had not been taking it consistently. Further workup was consistent with PJP pneumonia. Based on the patient’s poor compliance with atovaquone and chest CT findings, she was empirically started on treatment for PJP pneumonia with primaquine 30mg daily for 21 days, clindamycin 450mg every 6 hours for 21 days, prednisone 40 mg twice daily for 5 days, 40 mg daily for 5 days, then 20 mg daily for 11 days.  She started to show improvement in symptoms and hypoxia after starting this regimen. After completing PJP treatment she resumed prophylaxis with atovaquone 1500mg daily. Follow-up chest CT 3 months later was negative for infection.

Fidaxomicin PO 200 mg every 12 hours for 10 days was started for the C diff infection. Patient had persistent diarrhea after she completed the fidaxomicin course and C diff re-sent via stool sample and showed she was gene positive but protein negative, consistent with colonization. Stool sample also sent for Norovirus and showed she had a persistently positive norovirus PCR for a few months. She was also given additional IVIG.  Subsequently diarrhea improved and she only needed Imodium prn. After hospital discharge described above, cytomegalovirus (CMV) polymerase chain reaction (PCR), a molecular test used to detect and quantify CMV DNA, came back positive at 1100 IU/mL and she was given 2 weeks of valganciclovir 900mg BID. CMV PCR monitored weekly and was not detected after completing two weeks of treatment. CMV recurred a couple months later with a viral load of 21,000 IU/mL and she was restarted on valganciclovir 900mg PO BID. After one month of treatment, viral load was undetectable. She was decreased to valganciclovir 900mg PO daily for 3 months and then the valganciclovir was stopped. CMV PCR monitored monthly and CMV has not recurred. Of note, myeloma treatment with teclistamab was stopped after Cycle 9 dose given multiple infections.  She has remained in sCR with no other treatment in the two years since treatment has been held.