RO4929097 After Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma

Inclusion Criteria:

* Patients must have a diagnosis of multiple myeloma as defined below with staging based on the International Staging System:

  * Multiple myeloma - all three required (Note: these criteria identify stage 1B and stages II and IIIA/B myeloma by Durie/Salmon stage; stage 1A becomes smoldering or indolent myeloma):

    * Monoclonal plasma cells in the bone marrow ≥ 10% and/or presence of a biopsy-proven plasmacytoma
    * Monoclonal protein present in the serum and/or urine (if no monoclonal protein is detected \[non-secretory disease\], then \>= 30% monoclonal bone marrow plasma cells and/or biopsy-proven plasmacytoma is required)
    * Myeloma-related organ dysfunction (1 or more) (a variety of other types of end organ dysfunctions can occasionally occur and lead to a need for therapy; such dysfunction is sufficient to support classification as myeloma if proven to be myeloma related):

      * Calcium elevation in the blood (serum calcium \> 10.5 mg/L or upper limit of normal)
      * Renal insufficiency (serum creatinine \> 2mg/dL)
      * Anemia (hemoglobin \< 10 g/dL or 2 g \< normal)
      * Lytic bone lesions or osteoporosis (if a solitary \[biopsy-proven\] plasmacytoma or osteoporosis alone \[without fractures\] are the sole defining criteria, then \> 30% plasma cells are required in the bone marrow)
* Patients must have measurable disease

  * Patients with non-secretory multiple myeloma will be eligible only if the baseline serum free light chain level is elevated (\>= 10 mg/dL)
* For therapeutic treatment with RO4929097, patients must have peripheral blood stem cell collection of \>= 4.0 x 10\^6 cells/kg (patient's ideal body weight)
* ECOG performance status =\< 2, Karnofsky \>= 60%
* Estimated life expectancy of at least 12 weeks
* Absolute neutrophil count (ANC) \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Hemoglobin \>= 9.0 g/dL
* NOTE: Patients should not require chronic supportive growth factor administration or transfusions to meet treatment eligibility criteria (e.g., G-CSF for ANC eligibility)
* Serum creatinine =\< 2.0 mg/dL OR a measured creatinine clearance by 24-hour urine collection \>= 40 mL/min (a calculated creatinine clearance by Cockcroft-Gault formula is acceptable in lieu of a measured value)
* Total bilirubin within normal institutional limits
* AST (SGOT)/ALT SGPT) =\< 2.5 X institutional ULN
* Patients with uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia, defined as less than the lower limit of normal for the institution despite adequate electrolyte supplementation, are excluded from this study
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, and for at least 12 months post-treatment
* No requirement for routine use of hematopoietic growth factors (including granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, or interleukin-11) or platelet transfusions to maintain absolute neutrophil counts or platelet counts above the required thresholds for study entry

  * Use of erythropoietin-stimulating agents and red cell transfusions are also not permitted prior to initiation of RO4929097
* Patient must meet the institutional standard criteria for undergoing high-dose chemotherapy and autologous stem cell transplant
* No serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
* No uncontrolled intercurrent illness including, but not limited to:

  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * A history of torsades de pointes
  * Cardiac arrhythmia other than chronic, stable atrial fibrillation
  * Psychiatric illness/social situations that would limit compliance with study requirements
* No baseline QTcF \> 450 msec (male) or QTcF \> 470 msec (female)
* Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel are excluded

  * Subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded
* No condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedure affecting absorption, or active peptic ulcer disease) that impairs the ability to swallow and retain RO4929097
* Patients who have active hepatitis B or C, or have a history of liver disease, other forms of hepatitis or cirrhosis are ineligible
* HIV-positive patients on combination antiretroviral therapy are ineligible
* No second primary malignancy except most situ carcinoma (e.g., in situ carcinoma of the of the cervix, adequately treated non-melanomatous carcinoma of the skin) or other malignancy treated at least 3 years previously with no evidence of recurrence
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to RO4929097or other agents used in the study
* There are no limitations on type and amount of prior therapy with the following exception: patients who have had a solid organ transplant are ineligible

  * Acute toxicities of high-dose melphalan therapy must have resolved to the NCI-CTCAE version 4.0 grade 1 or less (with the exception of alopecia)
* Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible
* No concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4
* No concurrent drugs, food, supplements, or over-the-counter medications that may interfere with the metabolism of RO4929097, including ketoconazole and fresh-squeezed grapefruit juice
* Patients may not be receiving any other investigational agents
* Patients may not be receiving antiarrhythmics or other medications known to prolong QTc
* No other investigational or commercial agents or therapies may be administered with the intent to treat the patient's malignancy
* No patients who have had any chemotherapy or radiotherapy post-autologous stem cell transplant prior to entering the therapeutic arm of the study or those who have not recovered from the high-dose melphalan and autologous stem cell transplant
* For therapeutic treatment with RO4929097, the acute toxicities of the high-dose melphalan therapy must have resolved to the NCI-CTCAE version 4.0 Grade 1 or less (with the exception of alopecia)