Low Dose Dexamethasone and Thalidomide with Higher Frequency Zoledronic Acid (dtZ) for Multiple Myeloma.
Authors: Teoh Gerrard , Hwang William , Koh Liang Piu , Koh Mickey , Tan Daryl , Gullo Charles 
Published: April 2020

PURPOSE: To evaluate the activity of low dose dexamethasone (Dex) and thalidomide (Thal) plus higher frequency zoledronic acid (Zol) - dtZ - in patients with symptomatic multiple myeloma (MM) who are unable to tolerate standard doses of Dex and/or Thal and/or chemotherapy.

PATIENTS AND METHODS: Eighteen consecutive previously treated patients with symptomatic MM who were unable to tolerate conventional doses of Dex and/or Thal and/or chemotherapy were treated (on an intention to treat basis) with a low-toxicity regimen, dtZ; which comprises weekly Dex 20 mg OM for 4 days, Thal 50 mg ON, and three-weekly Zol 4 mg. Patients were treated for at least 3 months, and for up to 27.5 months. Five patients had complex karyotypes; including two patients with chromosome 13 deletion. The reasons for intolerance to standard therapy included pancytopenia, active viral hepatitis B, severe cardiovascular disease and recurrent severe infections.

RESULTS: The response rate was 78%, including good responses in 61%, and complete remissions in 22% of patients. All five patients with complex karyotypes showed good response to dtZ. The median time to remission was 8.2 months. Grade 2 toxicity included motor neuropathy (two patients) and infection (one patient); and grade 3 toxicity included motor neuropathy (two patients) and infection (one patient). No cases of deep venous thrombosis or pulmonary embolism were reported. All patients received calcium/vitamin D supplements; and mild, transient hypocalcemia was reported in only two patients. These were rapidly corrected with intravenous calcium gluconate. Mild, transient hepatitis was observed in two patients, which resolved spontaneously. Patients with active hepatitis B received lamivudine concurrently with no adverse effects. Contrary to expectation, more frequent dosing of Zol was associated with overall improved renal function (p&lt;0.01). Patients demonstrated accompanying improvements in β2-microglobulin, hypercalcemia, anemia, leucopenia, thrombocytopenia, hypoalbuminemia and normal immunoglobulins. Very few patients required blood component support. All patients reported an improvement in their quality of life and dramatically lower pain scores. There were 7-fold to 8-fold decreases in hospitalization and infection rates, with accompanying costs savings. Four patients with progressive disease were switched to other lines of therapy (including Velcade). Three patients defaulted follow-up but were alive and well at their final clinic attendance. No deaths were recorded during therapy.

CONCLUSION: The low-toxicity dtZ regimen was effective and well tolerated in patients with symptomatic MM who were unable to tolerate conventional doses of Dex and/or Thal and/or chemotherapy. It induced a high frequency of response, low incidence of serious irreversible toxicity, and good overall survival. Although the time to remission was slower than standard regimens, tolerance to therapy was excellent and patients enjoyed good quality of life. These observations support further studies of this promising combination, e.g. for patients with newly diagnosed MM.