Antineoplastics

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 62-year-old man exhibited lack of efficacy during treatment with ixazomib, cyclophosphamide and dexamethasone for IgD-λ multiple myeloma (MM). Subsequently, he developed grade II infusion reaction during treatment with daratumumab for IgD-λ MM.

In November 2018, the man first presented to the clinic with the chief complaint of palpitation and fatigue. After a thorough investigation a diagnosis of IgD-λ MM (International staging system stage 2) was made. Studies revealed serum M-protein of 2.85g/L, 24-hour urinary light chain of 0.12g, and chromosome 1q21 amplification and normal level of serum creatinine and lactate dehydrogenase. Further studies revealed moderate osteoporosis and no extramedullary lesions. Since, he had no remarkable comorbidities, he was considered transplant-eligible. Thereafter, he received induction chemotherapy with VTD regimen consisting of bortezomib, thalidomide, and dexamethasone. After four cycles of chemotherapy, he showed recovery in peripheral blood count and achieved very good partial response. To mobilize stem cells, etoposide in combination with filgrastim [recombinant human granulocyte colony stimulating factor] was adopted. A total of 8.25 × 10 ⁶/kg CD34+ cells were collected. After another two cycles of VTD chemotherapy, he received high-dose melphalan with autologous stem cell support and post transplant he achieved stringent complete remission (sCR). It was revealed that, he had a negative minimal residual disease. Thereafter, he started receiving maintenance therapy with lenalidomide. Until the outbreak of COVID-19, he was regularly followed up after which it was interrupted. Since, persistent sCR had been maintained during his follow-up prior to the COVID-19; according to the previous schedule at home, he continued to take lenalidomide. About after 3 months, he developed serious weakness due to which he visited clinic. Studies suggested a recurrence of IgD-λ MM. Additionally 3.6% myeloma cells were also detected in his peripheral blood. Further studies revealed a solid pulmonary nodule in the right lower lobe, which had been inconspicuous on his last studies. Thereafter, he received platelet transfusion. Afterwards, studies confirmed the diagnosis of moderately differentiated squamous lung cancer. However, on account of the worsening performance status and cytopenia, as well as due to concerns about the dissemination of circulating plasma cells, the lung cancer surgery was put on hold. Thereafter, chemotherapy for MM was planned aiming to improve his thrombocytopenia and fragility so that the risk of surgery could be reduced. Thereafter, due to its convenience during the COVID-19 pandemic, he started receiving chemotherapy regimen ICD consisting of oral ixazomib 4 mg at days 1, 8, 15; oral cyclophosphamide 400mg and oral dexamethasone 40mg at days 1, 8, 15, 22. However, he exhibited severe bone marrow suppression leading to persistent pancytopenia after chemotherapy. Therefore, lack of efficacy was considered for ixazomib, cyclophosphamide and dexamethasone. Thereafter, he received supportive care with hematopoietic growth factors and afterwards, he was hospitalized and received frequent blood transfusion. After 2 weeks from the last dose of cyclophosphamide, bone marrow examination revealed hypocellularity with evident myeloma cells of 68%. Worse still, he developed ineffective platelet transfusion and his bleeding symptoms had became more and more severe. Thereafter, he received salvage therapy with daratumumab 400mg at day 1, 800 mg at day 2, 1200 mg at days 8, 15, 22 [route not stated] in combination with dexamethasone. The chemotherapy was tolerated well; however he developed an episode of grade II infusion reaction attributed to daratumumab. Unexpectedly, after five doses of daratumumab, his blood counts including platelet recovered gradually and approached to a normal level. Moreover, studies did not reveal any myeloma cells and it was reported that IgD-M protein became unmeasurable. However, the size of the lung cancer had increased. Thereafter, he received laparoscopic lung lobectomy and lymph node dissection successfully. The postoperative studies again confirmed the diagnosis of lung cancer without lymph node metastasis. With the recovery from surgery, he resumed receiving daratumumab as consolidation chemotherapy for MM, but further treatments for both malignancies were cautiously determined through multi-disciplinary cooperation [duration of treatment to reaction onset and outcome not stated].